Diabetis 2

‫‪Diabetes Mellitus Type 2 Management‬‬
‫مديرية الشئون الصحية بالقليوبية‬

‫مستشفى كفر شكر المركزي‬
‫قسم الصيدلة اإلكلينيكية‬
‫‪Diabetes Mellitus Type 2 Management‬‬

‫‪.‬‬

Diabetes Mellitus Type 2 Management
DESCRIPTION
Diabetes mellitus (DM) type 2 is due to a progressive insulin secretory defect in the setting of insulin resistance.
ETIOLOGY [1] RISK FACTORS [1]
1. Peripheral insulin resistance and/or defective insulin secretion with increased hepatic gluconeogenesis 1. Gestational diabetes or history of baby with birth
2. Genetic factors: monogenic (e.g., PPARγ and insulin gene mutations) and polygenic weight ≥4 kg (9 lb)
3. Obesity (body mass index [BMI] ≥25 kg/m2) and visceral adiposity 2. Polycystic ovary syndrome (PCOS)
4. Gut microbiome changes 3. Hypertriglyceridemia or low high-density lipoprotein
5. Drug- or chemical-induced (e.g., glucocorticoids, highly active antiretroviral therapy [HAART], (HDL)—marker for insulin resistance
atypical antipsychotics, organ transplant immunosuppressants) 4. Ethnicity: African American, Latino, Native American,
6. Genetics Asian, and Pacific Islander
7. Genome-wide association studies in progress to identify associated genes; 50% concordance in 5. Sedentary lifestyle
monozygotic twins 6. Use of thiazides, antipsychotics, glucocorticoids.
8. Family history is strongly predictive of risk.
DIAGNOSIS [1]
HISTORY Polyuria, polydipsia, polyphagia, weight loss, weakness, fatigue, blurry vision, neuropathy, and
frequent infections
PHYSICAL-EXAM BMI, funduscopic exam, oral exam, cardiopulmonary exam, abdominal exam for hepatomegaly,
focused neurologic exam, and diabetic foot exam
DIFF-DIAGNOSIS Type 1 DM—low or absent insulin, pancreatic autoantibodies, ketosis
DM is one of the features of Cushing syndrome, acromegaly, and glucagonoma.
TESTS HbA1c ≥6.5% is diagnostic.
Hyperglycemic crisis + random plasma glucose ≥200 mg/dL (11.1 mmol/L) or
Fasting plasma glucose (FPG) ≥126 mg/dL (7.0 mmol/L) on two occasions or
2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) during oral glucose tolerance test (OGTT)
with 75-g glucose load
TESTS CONSIDERATIONS Screen patients with history of gestational diabetes for persistent diabetes/prediabetes 6 to 12
weeks postpartum with OGTT and at least every 3 years thereafter.
ASSOCIATED CONDITIONS [1]
Hypertension, dyslipidemia, metabolic syndrome, fatty liver disease, infertility, PCOS, acanthosis nigricans, hemochromatosis
1 American Diabetes Association 2 GeneBrandex 3 Micromedex 4 Applied therapeutics 5 Nurse’s Drug Handbook 6 BNF 7 Highlights of Insulin
Prepared by: Yousry Amin Rashad (clinical pharmacist) Nagwa Fawzy Mohammed (clinical pharmacist) Marwa Meselhy (clinical pharmacist)
References: American Diabetes Association , GeneBrandex, Micromedex, Nurse’s Drug Handbook, BNF, Highlights of Insulin
GENERAL-MEASURES [1]
1. Diabetic foot exam at every visit
2. Nephropathy: annual urine microalbumin-to-creatinine ratio if not on ACE-inhibitor
3. Retinopathy: annual diabetic eye exam
4. If 40 to 75 years old, begin a statin—moderate to high intensity based on ASCVD risk.
5. Low-dose aspirin in patients ≥50 years old with at least one additional CV risk factor and without risks for GI bleeding
6. Hypertension: goal BP <140/80 mm Hg (tighter control may be considered on individual basis)
7. Pneumococcal (PPSV-23) for all adults and pneumococcal conjugate vaccine (PCV-13) for patients >65 years (and some younger) and annual influenza
vaccine
FOLLOWUP-RECOMMENDATIONS [1]
MONITORING
Monitor glucose, HbA1c, BP, body weight, lipid profile, and renal and liver function q 3mo at first.
A1C twice a year for patients with well-controlled blood glucose and quarterly for patients with hyperglycemia or recent changes in therapy
PROGNOSIS
Normal lifespan with attention and prevention of comorbid complications
COMPLICATIONS
1. Emergencies: hyperosmolar coma, diabetic ketoacidosis (DKA), Charcot joints
2. Atherosclerotic CVD, peripheral vascular disease, stroke
3. Microvascular: peripheral neuropathy, proliferative retinopathy, erectile dysfunction, and diabetic CKD
4. Ophthalmic: blindness, cataracts, glaucoma, retinopathy
5. GI: nonalcoholic fatty liver disease, gastroparesis, diarrhea
6. Neurologic: autonomic dysfunction, foot ulcers and soft tissue infections
GENERAL PREVENTION [1]

 Maintenance of normal weight, or weight loss of 7% body weight
 Exercise 150 min/week
 Decrease in carbohydrates and overall caloric intake.
 Moderate-intensity exercise and resistance training are recommended.
 Higher intake of nuts, coffee, tea, and yogurt
 Use of metformin and thiazolidinediones (TZDs) in select patients with prediabetes
TREATMENT [1]
 Use patient-centered approach (individualized).
 Cornerstone of therapy is lifestyle modification and control of cardiovascular risk factors (particularly blood pressure and lipids).
A1C targets—according to ADA (recommendations NOT universally accepted as not fully evidence-based)
A1C <7.0: for those with a long life expectancy and no cardiovascular disease (CVD) who has had DM for a short duration and no history of hypoglycemia
A1C <8.0%: for those with a limited life expectancy, advanced micro- or macrovascular complications, extensive comorbidities, and a history of hypoglycemia or
long-standing DM in whom the general goal is difficult to attain.
ADA guidelines—preprandial glucose of 80 to 130 mg/dL and peak postprandial glucose of <180
mg/dL
ADA: FPG goal is <110 mg/dL (5.5 mmol/L) and 2-hour postprandial goal is <140 mg/dL.
Use drugs from different classes to achieve adequate control and limit side effects.
Use monotherapy unless A1C is ≥9% , dual therapy; if A1C ≥10%, BG 300 mg/Dl
Patient is symptomatic → insulin plus additional therapy
PHARMACOLOGIC THERAPY FOR TYPE 2 DIABETES [1]

 Metformin is the preferred initial pharmacologic agent for the treatment of type 2 diabetes.
 Once initiated, metformin should be continued as long as it is tolerated and not contraindicated;
other agents, including insulin, should be added to metformin.
 Early combination therapy can be considered in some patients at treatment initiation to extend the time to treatment failure.
 The early introduction of insulin should be considered if there is evidence of ongoing catabolism (weight loss), if symptoms of hyperglycemia are present, or when
A1C levels (>10% [86 mmol/mol]) or blood glucose levels (≥300 mg/dL [16.7 mmol/L]) are very high.
 Among patients with type 2 diabetes who have established atherosclerotic cardiovascular disease or indicators of high risk, established kidney disease, or heart
failure, a sodium–glucose cotransporter 2 inhibitor or glucagon-like peptide 1 receptor agonist with demonstrated cardiovascular disease benefit is
recommended.
PREGNANCY:
Diet, metformin, glyburide, and insulin are all options for treatment of gestational diabetes.
SURGERY
For patients with BMI >35 kg/m2, consider bariatric surgery.
MEDICATION
First-Line [1]
1) Biguanides
Metformin
Mechanism of action Efficacy
1. Decrease gluconeogenesis in liver Preferred first medication for most because it likely
2. Decrease intestinal absorption of glucose 1. Reduces risk of death
3. Increase peripheral glucose uptake and utilization 2. Promotes weight loss
i. Improve glucose use by skeletal muscle and adipose tissue (by 3. Improves insulin resistance
increasing glucose transport across cell membranes) 4. Some benefit in TG reduction
ii. Increase the number of insulin receptors on cell membranes and make Cause 1%–2% A1C reduction
them more sensitive to insulin
4. Decrease blood triglyceride and total cholesterol levels
Dose & Dose adjustment [2] Adverse Reactions [5] Precautions & Contraindications [5]
500 to 2,000 mg in divided doses or ER 1,000 to 2,000 mg every evening; CNS: Headache 1. Hypersensitivity to metformin or its
maximum effective dose 2,000 mg/day EENT: Metallic taste components
GI: Abdominal distention, anorexia, 2. Impaired renal function
Hepatic Impairment: [2] constipation, diarrhea, flatulence, 3. Metabolic acidosis
No dosage adjustment indigestion, nausea, vomiting 4. Use of iodinated contrast media within
 continued use of metformin in diabetic patients with liver dysfunction, HEME: decrease VIT B12 absorption, preceding 48 hours
including cirrhosis, has been used successfully and may be associated with Aplastic anemia, megaloblastic anemia, 5. Before surgery
a survival benefit in carefully selected patients; thrombocytopenia 6. severe acute illnesses (e.g., liver disease,
 use cautiously in patients at risk for lactic acidosis SKIN: Photosensitivity, rash cardiogenic shock, pancreatitis, hypoxia)
Other: Lactic acidosis, weight loss due to risk of lactic acidosis.
Renal Impairment: [2]
7. Metformin may be used in patients with
eGFR > 60 ml/min/1.73 m2: No dose adjustment
Do not cause hypoglycemia in nondiabetic stable heart failure (HF); avoid use in
eGFR > 45 to < 60 ml/min/1.73 m2: No dose adjustment
individuals or individuals with diabetes unstable or hospitalized patients with
eGFR 30 to 45 mL/minute/1.73 m2: Initiation of therapy: Use generally
when used as monotherapy. [4] heart failure [2]
not recommended. BUT can use reduced dose of ≤1,000 mg with close
monitoring
eGFR <30 mL/minute/1.73 m2: Use is contraindicated.
Drug interactions [5] Patient Counseling [5] Monitoring [5]
1. calcium channel blockers, corticosteroids, estrogens, 1. Give metformin tablets with food, at 1. Obtain HbA1c (twice yearly in stable patients and
isoniazid, nicotinic acid, oral contraceptives, phenothiazines, breakfast if taking drug once a day or at quarterly in unstable patients)
phenytoin, sympathomimetics, thiazide and other diuretics, breakfast and dinner if taking drug twice a 2. serum glucose, hematologic parameters
thyroid drugs: Possibly hyperglycemia day. 3. liver function tests (baseline)
2. Give E.R. tablets with evening meal; don’t 4. renal function tests (baseline and annually or more
2. cationic drugs (such as amiloride, cimetidine, digoxin, break or crush them. frequently in patients at risk for renal impairment)
morphine, procainamide, quinidine, quinine, ranitidine, 3. Withhold drug, as ordered, if patient 5. Check urine for glucose and ketones
triamterene, trimethoprim, vancomycin), nifedipine: becomes dehydrated or develops hypoxemia 6. Assess for signs and symptoms of vitamin B12
Increased blood metformin level or sepsis because these conditions increase and/or folic acid deficiency during therapy;
the risk of lactic acidosis. supplementation may be required
3. clofibrate, MAO inhibitors, probenecid, propranolol, 7. Assess for signs and symptoms of metabolic
rifabutin, rifampin, salicylates, sulfonamides, sulfonylureas: acidosis
Increased risk of hypoglycemia
Concerns related to adverse effects:

Lactic acidosis: [US Boxed Warning] [2] Vitamin B12 concentrations [2]
Symptoms & sings  Long-term metformin use is associated with vitamin
1. nonspecific symptoms (eg, malaise, myalgias, respiratory distress, somnolence, abdominal pain) B12 deficiency
2. elevated blood lactate levels (>5 mmol/L);  monitor vitamin B12 serum concentrations periodically
Risk factors for lactic acidosis with long-term therapy
1. patients with renal impairment,
2. concomitant use of certain drugs (eg, carbonic anhydrase inhibitors such as topiramate),
3. ≥65 years of age,
4. having a radiologic study with contrast,
5. surgery and other procedures,
6. hypoxic states (eg, acute heart failure)
7. hepatic impairment
Management
1. Discontinue immediately if lactic acidosis is suspected
2. prompt hemodialysis is recommended
2) Glucagon-like peptide-1 (GLP-1) receptor agonist (incretins)
analog of the hormone incretin (glucagon-like peptide 1 or 1. Risk of acute pancreatitis with GLP-1 agonists and DPP4 inhibitors.
GLP-1) which 2. Caution with use in CKD ≥ stage 4.
1. Increases glucose-dependent insulin secretion, 3. May exacerbate gastroparesis.
2. Decreases inappropriate glucagon secretion, 4. Cause modest weight loss.
3. Increases b-cell growth/replication, 5. GLP-1 analogs require insulin adjustment if patient on insulin.
4. Slows gastric emptying, and decreases food intake. Gallbladder disease: Use of glucagon-like peptide-1 (GLP-1) agonists may increase risk of gallbladder
and bile duct disease, including cholelithiasis and cholecystitis
Exenatide (Byetta, Bydureon) Liraglutide (Victoza, Saxenda) Dulaglutide (Trulicity) Lixisenatide (Adlyxin)
5 to 10 μg SC BID within 60 minutes before 0.6 mg/day SC for 1 week and then 0.75 to 1.50 mg weekly, up titration to 20 mcg SC qd;
meals and at least 6 hours apart or increase to 1.2, maximum 4.5 mg/week Administer within 1 hour before
exenatide (extended-release) 2 mg/week maximum 1.8 mg/day; Administer without regard to the 1st meal of the day.
Hepatic Impairment: [2] Administer without regard to meals or meals or time of day available in combination drug
No dosage adjustment time of day Soliqua (insulin glargine/
lixisenatide) —15 to 60 units SC
Dose & dose adjustment [2]
Renal Impairment: [2] Hepatic Impairment: [2] Hepatic Impairment: qd

Immediate release: No dosage adjustment [2] Hepatic Impairment: [2]
CrCl ≥30 mL/minute: No dosage adjustment No dosage adjustment
No dosage adjustment necessary;. Renal Impairment: [2]
CrCl <30 mL/minute: Use is not Mild to severe impairment: Renal Impairment: [2] Renal Impairment: [2]
recommended. No dosage adjustment necessary Mild to severe impairment: eGFR > 30 ml/min/1.73 m2:
ESRD, patients having dialysis: No dosage adjustment No dose adjustment
Use is not recommended. necessary eGFR 15-29 mL/minute/1.73
Extended release: m2: No dose adjustment
eGFR ≥45 mL/minute/1.73 m2: close monitoring for GI side
No dosage adjustment necessary. effects
eGFR <45 mL/minute/1.73 m2: eGFR <15 mL/minute/1.73 m2:
Use is not recommended. Use is contraindicated.
ESRD, patients having dialysis:
Use is not recommended
oral antidiabetics: Increased risk of hypoglycemia
interact
warfarin: Possibly increased INR with increased risk of bleeding

Drug
•If patient also takes a sulfonylurea, the sulfonylurea dosage may need to be decreased to reduce the risk of hypoglycemia.
ions
[5]
Usually, no dosage adjustment is needed for a patient taking metformin.

CNS: Asthenia, dizziness, headache, CNS: Dizziness, fatigue, headache ENDO: Hypoglycemia Back pain.
CV: Chest pain CV: Hypertension GI: diarrhea, nausea, cystitis.
EENT: Decreased taste EENT: Nasopharyngitis, sinusitis vomiting, Abdominal diarrhea. nausea. Vomiting,
ENDO: Hypoglycemia ENDO: Elevated calcitonin levels, thyroid C- distention or pain, dyspepsia, dyspepsia.
[5]
GI: Abdominal distention or pain, anorexia, cell hyperplasia, thyroid cancer flatulence, gastroesophageal Dizziness, drowsiness,
constipation, diarrhea, dyspepsia, flatulence, GI: Anorexia, constipation, diarrhea, dyspepsia, reflux, headache.
Adverse reactions
gastroesophageal reflux, indigestion, nausea, nausea, pancreatitis, slowed gastric emptying, Pancreatitis. Increased risk of infection.
pancreatitis (including life-threatening vomiting GU: Decreased renal [6]
hemorrhagic or necrotizing), vomiting GU: UTI function
GU: Decreased renal function MS: Back pain
RESP: Chronic pneumonitis RESP: Upper respiratory tract infection
SKIN: Diaphoresis, pruritus, rash, urticaria SKIN: Urticaria, Angioedema, anti-liraglutide
Anaphylaxis, angioedema, weight loss antibodies, influenza
 Should not be used in patients with  Liraglutide shouldn’t be given to a patient with  patient with a history of CONTRANDICATED IN
personal history/family history of a history of thyroid C-cell tumors, including thyroid C-cell tumors,  Ketoacidosis.
medullary thyroid cancer or multiple medullary thyroid carcinoma, or to patients including medullary  severe gastrointestinal
endocrine neoplasia (MEN) type 2 (black with multiple endocrine neoplasia syndrome thyroid carcinoma, or to disease
[5]
box warning) type 2 because drug may patients with multiple

 stimulate tumor growth. endocrine neoplasia
contraindications
 Hypersensitivity to exenatide or its syndrome type 2

Precautions &
components  Use liraglutide cautiously in patients with a

 Ketoacidosis history of pancreatitis because drug can cause
 type 1 diabetes mellitus pancreatitis and in patients with impaired
 with severe GI disease hepatic or renal function because drug effects
in these patients are unknown.
 Administer drug into patient’s thigh,  inject drug into his abdomen, thigh, or upper  Prior to initial use, store  Prior to initial use, store
abdomen, or upper arm. arm and to rotate sites to minimize injection under refrigeration at 2°C under refrigeration at 2°C
site reactions to 8°C to 8°C;
 Prior to initial use, store under  Prior to initial use, store under refrigeration at  after initial use, may store  after initial use, may store
refrigeration at 2°C to 8°C; 2°C to 8°C, after initial use, may store at 2°C at 2°C to 8°C or 15 to 30 at < 30 °C for 14 days [2]
 after initial use, may store at ≤25°C for 30 to 8°C or 15 to 30 °C for 30 days [2] °C for 14 days [2]
days [2]
 Once injected, continue to depress the button
[5]
until the dial has returned to 0 and for an

additional 6 seconds. Then, remove the needle.
Patient counseling
 less expensive and better tolerated than

exenatide.
 liraglutide isn’t recommended as 1ST line
therapy for patients with type 2 diabetes
mellitus not well controlled with diet and
exercise. It also isn’t a substitute for insulin
therapy
 Monitor patient’s blood glucose level.  Monitor patient’s serum calcitonin levels, as  Plasma glucose, HbA1c (at least twice yearly in patients
 If control decreases despite the patient’s indicated. who have stable glycemic control and are meeting
best efforts, drug may need to be  Be aware that elevations occur more often treatment goals; quarterly in patients not meeting
discontinued because of the possibility that when liraglutide dosage is 1.8 mg daily. treatment goals or with therapy change
anti-exenatide antibodies have formed.  Advise patient of possible risk of medullary  renal function (in patients reporting severe GI reactions)
 signs/symptoms of pancreatitis
[5]
thyroid cancer and need to report any

 Monitor patient for evidence of acute symptoms, such as a neck mass, dysphagia,
Monitoring
pancreatitis, such as persistent, severe dyspnea, or persistent hoarseness.

abdominal pain accompanied by vomiting,  Report persistent severe abdominal pain; it
especially when drug is started or dosage may radiate to the back and may be
increased. accompanied by vomiting.
 If pancreatitis is confirmed, expect to stop drug
3) SGLT2 inhibitors
1. Inhibit glucose reabsorption of filtered glucose from the tubular lumen by sodium glucose 1. Cause modest weight loss, but might increase risk of lower
cotransporter-2 (the main site of filtered glucose reabsorption ) inhibition in the proximal extremity amputation.
renal tubules. 2. Avoid in patients with peripheral vascular disease and foot ulcers.
2. lowers the renal threshold for glucose (RTG). [6]
So, increase urinary excretion of glucose, reduce plasma glucose concentrations.
Canagliflozin (Invokana) Dapagliflozin (Farxiga) Empagliflozin (Jardiance)

CONTRA-INDICATIONS
Contraindications
 Ketoacidosis
Precautions &
CAUTIONS
[6]
 Cardiovascular disease (risk of hypotension).

 elderly (risk of hypotension).
 elevated haematocrit.
 history of hypotension
 may increase the risk of lower-limb amputation (mainly toes) in patients with type2 diabetes. So, preventive foot care is important for all patients with
counseli
Patient
ng [5]
diabetes.
 do not restart treatment with any SGLT2 inhibitor in patients who experienced DKA during use, unless another cause for DKA was identified and resolved
 Determine renal function before treatment and at least annually thereafter, and before initiation of concomitant drugs that reduce renal function and
periodically thereafter.
 volume status (eg, BP, hematocrit, electrolytes);
Monitoring
 monitor for genital mycotic infections and UTI;

 assess patients presenting with fever or malaise along with genital or perianal pain, tenderness, erythema
100 to 300 mg single dose before 5 to 10 mg daily; avoid use if eGFR <60. 10 to 25 mg daily; avoid use if eGFR <45;
breakfast shown to reduce cardiovascular morbidity and
administered with or without food in the morning death
May be administered with or without Hepatic Impairment: [2]
food. No dosage adjustment administered with or without food in the
It is recommended to take before the first morning
meal of the day Renal Impairment: [2]
eGFR ≥45 mL/minute/1.73 m2: Hepatic Impairment: [2]
Hepatic Impairment: [2] No dosage adjustment necessary. No dosage adjustment
Mild-to-moderate impairment (Child- eGFR 30 to <45 mL/minute /1.73 m2:
[2]
Pugh class A, B): No dosage adjustment Heart failure: No dosage adjustment necessary. Renal Impairment: [2]
necessary. Diabetic kidney disease (off-label use): eGFR ≥30 mL/minute/1.73 m2:
Dose & Dose adjustment
Severe impairment (Child-Pugh class No dosage adjustment necessary No dosage adjustment necessary
C): Use not recommended (has not been Heart failure with reduced ejection fraction: No dosage eGFR <30 mL/minute/1.73 m2:
studied). adjustment necessary. use is contraindicated; however, in patients
Proteinuric chronic kidney disease (off-label use): No dosage previously established on empagliflozin, some
Renal Impairment: [2] adjustment necessary experts continue use off label at a dose of 10
eGFR ≥60 mL/minute/1.73 m2: No eGFR <30 mL/minute/1.73 m2: mg once daily
dosage adjustment necessary. Hyperglycemia: Use is contraindicated. Hemodialysis, intermittent (thrice weekly):
eGFR 30 to <60 mL/minute /1.73 m2: Heart failure: there is insufficient data to support a dosage Use is contraindicated
100 mg once daily. recommendation. Peritoneal dialysis: Use is contraindicated
eGFR <30 mL/minute/1.73 m2 Diabetic kidney disease (off-label use): should not be initiated
not recommend initiation of therapy; in patients with an eGFR <25 to 30 mL/minute/1.73 m2
however, patients previously established Heart failure with reduced ejection fraction: there is
on canagliflozin may continue 100 mg insufficient data
once daily. Proteinuric chronic kidney disease (off-label use): No dosage
adjustment necessary for eGFR ≥25 mL/minute/1.73 m2; not
End-stage renal disease, hemodialysis: studied in patients with an eGFR <25 mL/minute/1.73 m2
Use is contraindicated. End-stage renal disease, hemodialysis: Use is contraindicated.
oral antidiabetics: Increased risk of hypoglycemia
interactio
Drug
ns
 constipation.
 dyslipidemia.
 hypoglycemia (in combination with insulin or sulphonylurea).
 increased risk of infection.
 nausea.
 thirst.
Adverse reactions
 urinary disorders.
 Dehydration.
 dizziness postural.
 hypotension
 lower limb amputations.
 renal failure.
 skin reactions.
 Syncope
 genital mycotic infections,
 UTI
Incretin-Based Therapies
 Incretins are insulinotropic hormones secreted from specialized neuroendocrine cells in the small intestinal mucosa in response to carbohydrate ingestion and
absorption.
 The two hormones accounting for most incretin effects are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1).
 GIP and GLP-1 stimulate pancreatic β-cells in a glucose-dependent manner, contributing to the early-phase insulin response.
 GLP-1 also inhibits pancreatic α-cells, thus reducing glucagon secretion and hepatic glucose production.
 Incretin action is efficient, but short lived. As they enter the blood vessels, incretins undergo rapid metabolism via proteolytic cleavage by dipeptidyl peptidase-4
(DPP-4) to inactive metabolites.
4) Dipeptidyl peptidase-4 inhibitors

 Sitagliptin inhibits dipeptidyl peptidase-4 (DPP-4) enzyme  Weight neutral with minimal risk for hypoglycemia;
resulting in prolonged active incretin levels.  Dose adjustments in renal function decline with exception of linagliptin.
 Alogliptin and saxagliptin are associated with heart failure, but sitagliptin is likely not.
Sitagliptin (Januvia) Saxagliptin (Onglyza) Vildagliptin (Vildagluse) Linagliptin Alogliptin (Nesina)

CONTRAINDICATED WITH
Contraindic
Precautions
ations [6]
Diabetic ketoacidosis,
&
CAUTIONS
History of pancreatitis.
Not recommended in moderate to severe heart failure (limited experience)
Instruct patient to stop taking drug and report persistent severe abdominal pain, possibly radiating to the back and accompanied by vomiting.
counseli
Patient
ng [5]
 Monitor patient for hypersensitivity reactions that, although uncommon, may be severe.
Monitoring
 If present, notify prescriber and expect to be discontinue.

 Monitor patient’s blood glucose level & Watch for hypoglycemia in patients taking antidiabetics, such as sulfonylureas
 Obtain a serum creatinine level, before starting therapy and then periodically thereafter to monitor patient’s renal function.
100 mg/day 2.5 mg/day, maximum 5 50 mg once or twice daily (max: 5 mg/day 25 mg/day
Administer without regard to mg/day 100 mg /day) Administer without Administer without regard to meals
meals Administer without regard to Administer without regard to regard to meals
meals meals
Hepatic Impairment: [2]
Hepatic Impairment: Hepatic Impairment: Hepatic Impairment: [2] Hepatic No dosage adjustment
[2] [2] Use is not recommended in Impairment: [2]
No dosage adjustment No dosage adjustment patients with preexisting hepatic No dosage
impairment, including patients adjustment
with pretreatment ALT or AST
[2]
>2.5 x ULN; discontinue use in

patients who develop ALT or

AST >3 x ULN during therapy.
Renal Impairment: [2] CrCl ≥60 mL/minute:
Renal Impairment: Renal Impairment: Renal No dosage adjustment necessary;.
[2] eGFR ≥60 mL/minute/1.73 m2
[2]
eGFR > 45 ml/min/1.73 m2: (or CrCl ≥50 mL/minute): No Impairment: CrCl >30 - <60 mL/minute:
eGFR > 45 ml/min/1.73 m2: [2] 12.5 mg once daily
No dose adjustment dosage adjustment necessary.
No dose adjustment No dosage CrCl >15 - <30 mL/minute:
eGFR >30 to < 45 eGFR < 45 mL/minute /1.73
eGFR 15 to <60 adjustment 6.25 mg once daily
mL/minute /1.73 m2: 50 mg m2: 2.5 mg once daily
mL/minute/1.73 m2 (or CrCl ESRD, (CrCl <15 mL/minute ),
once daily ESRD, patients having
<50 mL/minute): Initial and patients having dialysis:
eGFR <30 mL/minute/1.73 dialysis:
maximum: 50 mg once daily. 6.25 mg once daily, administer
m2: 25 mg once daily 2.5 mg once daily, administer
without regard to timing of
postdialysis
ESRD requiring hemodialysis: hemodialysis
Initial and maximum: 50 mg
once daily; not significantly
dialyzed
 ACE inhibitors,  aprepitant, diltiazem,  ACE inhibitors, disopyramide,  ACE inhibitors,  Caution with use in combination
disopyramide, fibric acid erythromycin, fluconazole, fibric acid derivatives, disopyramide, fibric with both metformin and
derivatives, fluoxetine, fosamprenavir, verapamil: fluoxetine, sulfonylureas: acid derivatives, pioglitazone—risk of
sulfonylureas: Possibly Possibly increased plasma Possibly increased fluoxetine, hypoglycaemia (dose of metformin
increased hypoglycemic saxagliptin level sulfonylureas: or pioglitazone may need to be
Drug interactions [5]
effects  atazanavir, clarithromycin, Possibly increased reduced).

 beta blockers: Possibly indinavir, itraconazole,
prolonged hypoglycemia or ketoconazole, nefazodone,
promotion of hyperglycemia nelfinavir, ritonavir,
 digoxin: Slightly increased saquinavir, telithromycin:
plasma digoxin level Increased plasma saxagliptin
 estrogens, oral level
contraceptives, phenytoin,  sulfonylureas: Increased risk
progestines, thiazide of hypoglycemia
diuretics, triamterene:
Possibly decreased
hypoglycemic effects
CNS: Headache CNS: Headache ▶ Common or very common ▶Uncommon ▶ Common or very common
EENT: Nasopharyngitis EENT: Sinusitis, Dizziness Cough  Abdominal pain.
GI: Abdominal pain, acute nasopharyngitis ▶ Uncommon nasopharyngitis  gastrooesophageal reflux
Adverse reactions [5]
pancreatitis, diarrhea, ENDO: Hypoglycemia  Arthralgia. Constipation. ▶ Rare or very rare disease.
elevated hepatic enzymes, GI: Abdominal pain,  headache Angioedema.  headache.
nausea, vomiting gastroenteritis, vomiting  hypoglycaemia. skin reactions  Increased risk of infection.
RESP: Upper respiratory GU: Elevated plasma  peripheral edema [6] ▶ Frequency not  skin reactions
tract infection creatinine level, UTI known ▶ Frequency not known
SKIN: Cutaneous vasculitis, HEME: Lymphopenia Pancreatitis [6] Angioedema.
rash, Stevens-Johnson RESP: URTI  hepatic function abnormal.
syndrome, urticaria, SKIN: Rash, urticaria,  pancreatitis acute.
Anaphylaxis, angioedema Peripheral edema, facial  Stevens-Johnson syndrome
edema [6]
Second-Line [1]
1) Insulin
Classification of Insulin according to its source: [7]
Rapid acting Human insulin analogues– The difference between u-40 & u-100 insulin syringes [7]
insulin Humalog ® ( lispro)/ (NovoRapid®),Novolog ® (  If you use U-40 insulin , you should choose a U-40 syringe
aspart)/Fiasp® (aspart) /Apidra® (glulisine)  If you use U-100 insulin, you should choose a U-100 syringe
Short acting Human sources –  U-100 has 100 units per milliliter and U-40 has 40 units per
("Regular") Humulin ® R (regular), Actrapid®, milliliter
insulin Novolin ® R( regular), and Velosulin ® BR (regular)
Pork sources -Iletin II ® (regular) and Purified Pork  Dosing errors can be costly or even deadly. Just choose the right
regular syringe for the insulin
Intermediate Human sources –  the same volume of U-100 insulin having 2.5 more units in it than
acting insulin Humulin ® N (NPH), Insulatard®, U-40 insulin.
Humulin ® L (Lente),Novolin ® L (Lente), and Novolin  Calculate the amount of U-40 insulin administered in a U-100
® (NPH) syringe by multiplying the amount of units on the insulin bottle
Pork sources - Iletin ® II, Iletin II ® NPH, Purified times 2.5. Draw that amount into the U-100 insulin syringe. For
Pork Lente and Purified NPH
example, if your prescription is for 6 units of U-40 insulin, 6 x
Long-acting Human source – Humulin ® U (Ultralente)
insulin Human insulin analogue – Lantus ® , Tougeo® , 2.5= 15. Draw up the insulin in the U-100 syringe to the 15 unit
Vivaro® (glargine) / Levemir® ( detemir)/ Tresiba® marking.
(degludec)
Side Effects
1) Severe hypoglycemia
2) Weight gain
3) Lipodystrophy, loss of fatty tissue where the insulin is injected
4) Allergic reactions- in rare cases -that include swelling, or edema
Classification according to Onset, Peak and Duration of action: [7]
Role in Blood Sugar Management Duration Peak Onset Brand Names

Rapid-Acting
Rapid-acting insulin covers insulin needs for meals eaten 3-5 hours 30-90 min 15-30 min. Humalog (lispro)
at the same time as the injection. 3-5 hours 40-50 min. 10-20 min. Novolog (aspart)
This type of insulin is used with longer-acting insulin.
for meals eaten within 15 min 3 to 5 hrs 1 and 3 hrs 4 min Fiasp (aspart)
1-2½ hours 30-90 min. 20-30 min. Apidra (glulisine)
Short-Acting
Short-acting insulin covers insulin needs for meals eaten 5-8 hours 2-5 hours 30 min. -1 hour Regular (R) humulin , Actrapid
within 30-60 minutes or novolin
2-3 hours 2-3 hours 30 min.-1 hour Velosulin
Intermediate-Acting
Intermediate-acting insulin covers insulin needs for about 18-24 hours 4-12 hours 1-2 hours NPH Humulin (N), Insulatard
half the day or overnight. This type of insulin is often 18-24 hours 3-10 hours 1-2½ hours Lente (L)
combined with rapid- or short-acting insulin.
Long-Acting
Long-acting insulin covers insulin needs for about one 20-36 hours 10-20 hours 30 min.-3 hours Ultralente (U)
full day. This type of insulin is often combined, when 20-24 hours No peak time 1-1½ hour Lantus, Vivaro, Tougeo,
needed, with rapid- or short-acting insulin. Basaglar (glargine)
Up to 24 hours 6-8 hours 1-2 hours Levemir (detemir)
24 hours No peak time 30 – 90 min Tresiba (degludec)
Pre-Mixed**
These products are generally taken twice a day before 14-24 hours 2-4 hours 30 min. Humulin 70/30
mealtime. Up to 24 hours 2-12 hours 30 min. Novolin 70/30
Up to 24 hours 1-4 hours 10-20 min. Novolog 70/30
18-24 hours 2-5 hours 30 min. Humulin 50/50
16-20 hours 30 min.-2½ hours 15 min. Humalog mix 75/25
Storage of Insulin [7]
Not in-use (unopened) (vial, cartridge, pen) In-use (opened) (vial) In-use (opened) (Cartridge, pen)
Rapid-Acting insulin
1 Novorapid® 2 – 8°C up to expiry date stored at room temp. up to 28 Cartridge must be stored at room temp. up to
Vial, cartridge, pen days. 28 days Do not refrigerate
Do not refrigerate Pen 2 – 8°C or at room temp., up to 28 days
2 Apidra® 2 – 8°C up to expiry date. If left at room temp. can be in 2 – 8°Cor at room must be stored at room temp. up to 28 days.
Vial, pen used up to 28 days temperature, up to28 days Do not refrigerate
3 Humalog® 2 – 8°C up to expiry date in 2 – 8°C or at room must be stored at room temp. up to 28 days.
Vial, cartridge, pen or at room temp. up to 28 days temperature, up to28 days Do not refrigerate
4 Fiasp® Cartridge in 2 – 8°C or Cartridge must be stored at room temperature
Vial, cartridge, pen Vial, Pen 2 – 8°C up to expiry date at room up to 28 days.
or at room temp. up to 28 days temperature, up to28 days Do not refrigerate
Pen 2 – 8°C or at room temp., up to 28 days
Short-Acting insulin
5 Actrapid® 2 – 8°C up to expiry date at room temperature below at room temperature below 25°C for 6 weeks.
Vial, cartridge, pen 25°C for 6 weeks. Do not refrigerate
Do not refrigerate
6 Humulin R® 2 – 8°C up to expiry date in 2 – 8°C or at room must be stored at room temperature up to 28
Vial, cartridge, pen Vial may be stored at room temperature, up to31 days temperature, up to31 days days
Do not refrigerate
Intermediate-Acting insulin
7 Insulatard® 2 – 8°C up to expiry date at room Temp.(<25°C) up to at room Temperature (< 30°C) up to 6 weeks
Vial, cartridge, pen 6 weeks Do not refrigerate Do not refrigerate
8 Humulin N® 2 – 8°C up to expiry date 2 – 8°Cor at room Cartridge at room temperature for 21 days
Vial, cartridge, pen Vials at room temp. for 31 days temperature, up to31 days Pen at room temperature for 14 days
Cartridge at room temp. for 21 days Do not refrigerate
Not in-use (unopened) (vial, cartridge, pen) In-use (opened) (vial) In-use (opened) (Cartridge, pen)
Long-Acting insulin
9 Lantus® 2 – 8°C up to expiry date or 2 – 8°C or at room at room Temperature (< 30°C) up to 28 days
Vial, pen at room temperature for 28 days temperature for 28 days Do not refrigerate
10 Basalgar® 2 – 8°C up to expiry date or ----------- at room Temperature (< 30°C) up to 28 days
Pen at room temp. for 28 days Do not refrigerate
11 Tougeo® 2 – 8°C up to expiry date ----------- at room temperature for 42 days
Pen Do not refrigerate
12 Vivaro® 2 – 8°C up to expiry date ----------- at room temp- for 28 days
Pen Do not refrigerate
13 Levemir® 2 – 8°C up to expiry date 2 – 8°C or at room at room Temperature (< 30°C) up to 42 days
Vial, cartridge, pen If left at room temperature can be used up to 42 days temperature for 42 days Do not refrigerate
14 Tresiba® 2 – 8°C up to expiry date 2 – 8°C or at room temperature up to 8 weeks
Pen If left at room temperature can be used up to 8 weeks
Pre-Mixed insulin
15 Mixtard mix® 2 – 8°C up to expiry date at room temperature, up to 6 at room temperature, up to 6 weeks
Vial, cartridge, pen weeks Do not refrigerate
16 Humulin mix® 2 – 8°C up to expiry date (vial, Cartridge) Prefilled pen
Vial, Pen *Vials may be stored at room temp. for 31 days 2 – 8°C or at room at room temperature for 10 days
*Pen may be stored at room temp. for 10 days temperature, up to 31 days Do not refrigerate
17 Humalog® Mix 2 – 8°C up to expiry date 2 – 8°C or Prefilled pen
Vial, Pen *Vials may be stored at room temp. for 28 days at room at room temperature for 10 days
*Pen may be stored at room temp. for 10 days temperature, up to 28 days Do not refrigerate
18 Novomix ® 2 – 8°C up to expiry date ----------- below 30°C for up to 28 days
cartridge, pen Do not refrigerate
19 Xultophy® pen 2 – 8°C up to expiry date ----------- 2 – 8°C or at room temperature for 21 days
20 Ryzodog® 2 – 8°C up to expiry date ----------- Cartridge at room temperature up to 28 days
cartridge, pen Do not refrigerate
Pen 2 – 8°C or at room temperature for 28 days
Therapeutic Insulin Management of Type 1 DM [7] Changing from oral DM medications to insulin- only management [7]
Weight-based estimate if insulin naïve (new, 1sttime) In case of failure of oral therapy, you will be shifted to insulin
0.3–0.6 unit/kg/day a. follow NPH/regular insulin or basal/bolus approach similar to type 1 DM
A) If total requirements less than 30 IU … Will give single dose of b. The TDI requirements in type 2 DM are usually higher than in type 1 DM.
long acting insulin
B) If total requirements more than 30 IU …. Will give mixed insulin, Changing from NPH to long-acting insulin (either glargine or detemir) [2]
as the following: From To Dose conversion
Once-daily NPH Glargine Unit-per-unit basis
One common approach (NPH and regular insulin). Mixtard 70/30
Twice-daily NPH Glargine Use 80% of the total daily dose of NPH
2/3 before morning meal ---- (2/3 as NPH, 1/3 as regular insulin
insulin
1/3 before evening meal --- (2/3 as NPH, 1/3 as regular insulin)
Once-daily insulin Toujeo Unit-per-unit basis
detemir
a. Regular- and short-acting insulin target postprandial glucose
Twice-daily insulin Toujeo Use 80% of the total daily dose of detemir
concentrations.
detemir
b. Intermediate- and long-acting insulin target fasting glucose
Once- daily lantus Once-daily toujeo Unit-per-unit basis
concentrations
Once-daily Toujeo Once-daily Lantus Use 80% of the total daily dose of Toujeo
(300 units/ml)
NPH Detemir Unit-to-unit basis
2) Amylinomimetic
Pramlintide (Symlin)
 Pramlintide is a synthetic analogue of amylin, a naturally occurring neuroendocrine hormone secreted with i. A 0.5%–1% reduction in A1c
insulin by pancreatic beta cells. ii. Very effective at controlling postprandial glucose
 Slows the rate at which food is released from stomach to small intestine, thus reducing initial postprandial excursions
rise in serum glucose level.
 Pramlintide also suppresses glucagon secretion and promotes satiety, thus furthering weight loss, which
also lowers serum glucose level.
Dose & Dose adjustment [2] Adverse Reactions [5] Precautions & Contraindications [5] Drug interactions [5]
60 to 120 μg SC immediately before every CNS: Dizziness, fatigue, headache Contraindicated with Drugs that alter GI motility (such
major meals EENT: Blurred vision, pharyngitis 1. glycosylated hemoglobin > 9%, as anti-cholinergics) or
ENDO: Insulin-induced hypoglycemia 2. recurrent severe hypoglycemia that slow intestinal absorption of
Hepatic Impairment: [2] GI: Abdominal pain, anorexia, nausea, required assistance during past 6 nutrients (such as alpha-
No dosage adjustment MS: Arthralgia months glucosidase inhibitors):
RESP: Coughing 3. hypoglycemia unawareness Altered effects of these drugs
SKIN: Diaphoresis 4. gastroparesis
Other: Hypersensitivity reactions; local 5. concurrent therapy with drugs that
CrCl > 15 ml/min: No dose adjustment
injection site reaction, such as redness, stimulate GI motility
ESRD: No dose adjustment
swelling, or pruritus 6. pediatric patients.
Patient counseling [5] Monitoring [5]

 Expect that certain patients won’t be prescribed pramlintide  Monitor patient’s pre- and post-meal blood glucose levels regularly
because its risks may outweigh its benefits. These include  For 3 hours after each dose of pramlintide, monitor patient closely for hypoglycemia, Effects may
patients with poor compliance with current insulin regimen, include hunger, headache, sweating, tremor, irritability, and trouble concentrating.
poor compliance with monitoring blood glucose level,  Although pramlintide doesn’t cause hypoglycemia, it’s use with insulin increases the risk of
 Before pramlintide therapy starts, make sure patient’s pre- insulin-induced severe hypoglycemia
meal insulin dosage has been reduced by 50%  Closely monitor patients taking oral antidiabetics, ACE inhibitors, disopyramide, fibrates,
fluoxetine, MAO inhibitors, pentoxifylline, propoxyphene, salicylates, or sulfonamide antibiotics
because of an increased risk of hypoglycemia.
3) α-Glucosidase inhibitors
Inhibits action of alpha-amylase and alpha-glucoside enzymes. i. 0.5%–0.8% reduction in A1c
Slows the absorption of glucose from the intestine into the bloodstream by slowing the ii. Targets postprandial glucose excursions
breakdown of large carbohydrates (disaccharide) into smaller absorbable sugars iii. May not be as effective in patients using low-carbohydrate diets
(monosaccharide)
Acarbose (Precose) Miglitol (Glyset)

25 to 100 mg TID 25 to 100 mg TID
Administer with the 1st bite of each meal Administer with the 1st bite of each meal
Hepatic Impairment: [2] Hepatic Impairment: [2]
No dosage adjustment No dosage adjustment
But contraindicated in cirrhosis
[2]

Renal Impairment: [2] CrCl ≥25 mL/ minute: no dosage adjustments
Serum creatinine ≤2 mg/dL or CrCl ≥25 mL/ minute: no dosage adjustments
Serum creatinine >2 mg/dL or CrCl <25 ml/minute: Use is not
Serum creatinine >2 mg/dL or CrCl <25 ml/minute: Use is not recommended recommended
 calcium channel blockers, digestive enzymes (such as pancreatin), diuretics,  digestive enzyme preparations, intestinal adsorbents (activated
Drug interactions
estrogen, intestinal adsorbents (such as activated charcoal), isoniazid, nicotinic charcoal): Decreased miglitol effects
acid, oral contraceptives, phenothiazines, phenytoin, sympathomimetics, thyroid  digoxin: Decreased blood digoxin level
 propranolol, ranitidine: Decreased bioavailability of these drugs
[5]
hormones: Possibly decreased therapeutic effects of acarbose

 digoxin: Decreased serum level and therapeutic effects of digoxin
 insulin, sulfonylureas: Decreased insulin action, possibly increased risk of hypo-
 glycemia
CV: Edema GI: Abdominal pain, diarrhea, flatulence, hepatotoxicity
reactions
Adverse
GI: Abdominal distention and pain, diarrhea, flatulence, hepatitis, hepatotoxicity, HEME: Low serum iron level
[5]
ileus, jaundice SKIN: Rash (transient)

SKIN: Erythema, exanthema, rash, urticaria
Acarbose (Precose) Miglitol (Glyset)
Contraindicated in: Contraindications:
Contraindications
 Chronic intestinal disease, cirrhosis, colonic ulceration,  Acute or chronic bowel disorder,
Precautions &
 conditions that may deteriorate because of increased gas formation in intestines,  Diabetic ketoacidosis
 digestive or absorption disorders  renal insufficiency
[6]
 history of bowel obstruction  hypersensitivity to miglitol

 inflammatory bowel disease
 diabetic ketoacidosis,
 hypersensitivity to acarbose
Be aware about signs of: Drug must have arrived at site of enzymatic action when carbohydrates
counseli
Patient
ng [5]
 hypoglycemia reach small intestine.

 liver problems (dark urine, lack of appetite, nausea, abdominal pain, light-
colored stools, vomiting, or yellow skin or eyes)
 Monitor glycosylated hemoglobin level as ordered every 3 months for first year to •Review patient’s HbA1Clevel, as appropriate, to monitor long-term
Monitoring
 evaluate glucose control and patient compliance. glucose control.

 Monitor hematocrit and serum AST level every 3 months during first year of •Monitor patient for evidence of overdose,such as transient increases in
therapy and periodically thereafter, as ordered, because acarbose may decrease abdominal discomfort, diarrhea, and flatulence (but not hypoglycemia).
hematocrit and increase serum AST level.
4) Diphenylalanine derivatives (Meglitinide analog)
Mechanism of Action Efficacy
 stimulates the release of insulin from functioning beta cells of the pancreas. i. 0.5%–1.5% A1c reduction (repaglinide
 In patients with type 2 diabetes mellitus, a lack of functioning beta cells more potent than nateglinide)
 diminishes blood levels of insulin and causes glucose intolerance. ii. Most effective on postprandial glucose
 By interacting with the adenosine triphosphatase (ATP)–potassium channel on the beta cell membrane, nateglinide excursions (change in glucose from
prevents potassium (K+) from leaving the cell. This causes the beta cell to depolarize and the cell membrane’s calcium before and after meal)
channel to open.
 Consequently, calcium (Ca++) moves into the cell and insulin moves out of it.
 The extent of insulin release is glucose dependent; the lower the glucose level, the less insulin is secreted from the cell.
similar to sulfonylureas but more rapid onset and shorter duration of activity
Repaglinide (Prandin) Nateglinide (Starlix)
0.5 to 4.0 mg 2, 3 or 4 times/ day 60 to 120 mg TID
[2]
Administer within 30 min before meals Administer within 30 min before meals
Hepatic Impairment: [2] Hepatic Impairment: [2]

No dosage adjustment No dosage adjustment
Renal Impairment: [2] Renal Impairment: [2]

CrCl ≥40 mL/minute: No dosage adjustment necessary. Mild to moderate impairment: No dosage adjustment necessary.
CrCl 20 to 40 mL/minute: Initial: 0.5 mg with meals; Severe impairment:
titrate carefully. if eGFR <30 mL/minute/1.73 m2: Initiate conservatively at 60 mg 3 times daily with meals
CrCl <20 mL/minute: no dosage adjustments if eGFR <15 mL/minute/1.73m2 Use with caution, due to potential accumulation of a
Hemodialysis: no dosage adjustments metabolite with hypoglycemic activity
Contraindicated in: Contraindicated with
Contraindicati
Precautions &
 Concurrent therapy with gemfibrozil  Diabetic ketoacidosis

ons [6]
 diabetic ketoacidosis  hypersensitivity to nateglinide

 hypersensitivity to repaglinide  type 1 diabetes mellitus
 severe hepatic or renal impairment
 type 1 diabetes mellitus
Repaglinide (Prandin) Nateglinide (Starlix)
 barbiturates, carbamazepine, rifampin, troglitazone:  corticosteroids, sympathomimetics, thiazide diuretics, thyroid products: Possibly reduced
Possibly increased repaglinide metabolism  hypoglycemic effects of nateglinide
 beta blockers, chloramphenicol, clarithromycin, MAO  MAO inhibitors, nonselective beta-adrenergic blockers, NSAIDs, salicylates: Possibly
inhibitors, NSAIDs, oral anticoagulants, probenecid, additive hypoglycemic effects of nateglinide
salicylates, sulfonamides: Enhanced hypoglycemic effects

 calcium channel blockers, corticosteroids, diuretics,
estrogens, isoniazid, niacin, oral contraceptives,
phenothiazines, phenytoin, sympathomimetics, thyroid
hormones: Possibly loss of glucose control
 erythromycin, ketoconazole, miconazole: Possibly
inhibited repaglinide metabolism
 gemfibrozil: Increased blood repaglinide level, resulting in
enhanced and prolonged blood glucose–lowering effects
 NPH insulin: Possibly increased risk of angina
CNS: Headache CNS: Dizziness
CV: Angina ENDO: Hypoglycemia
Adverse reactions [5]
EENT: Rhinitis, sinusitis GI: Cholestatic hepatitis, diarrhea, elevated liver enzyme levels, jaundice
ENDO: Hypoglycemia MS: Accidental trauma, arthropathy, back pain
GI: Diarrhea, elevated liver enzymes, hepatitis, nausea, RESP: Bronchitis, cough, upper respiratory tract infection
pancreatitis SKIN: Pruritus, rash, urticaria
HEME: Hemolytic anemia, leukopenia, thrombocytopenia Other: Flulike symptoms
MS: Arthralgia, back pain
RESP: Bronchitis, upper respiratory tract infection
SKIN: Alopecia, Stevens-Johnson syndrome, Anaphylaxis
•Be aware that repaglinide shouldn’t be used with NPH Monitor fasting glucose and HbA1clevels periodically
counseling [5]
insulin because the combination may increase the risk of

Patient
angina.
•Review signs and symptoms of hyperglycemia and
hypoglycemia
•Expect to check HbA1clevel every 3 months
5) Sulfonylurea
Mechanism of Action
Stimulates insulin release from beta cells in pancreas. Bind to receptors on pancreatic β-cells, leading to membrane depolarization with
Increase peripheral tissue sensitivity to insulin, either by enhancing insulin subsequent stimulation of insulin secretion (insulin secretagogue)
binding to cellular receptors or by increasing the number of insulin receptors. Block K channels >> membrane depolarization >> Ca influx >> secretion
Glimepiride (Amaryl) Glipizide (Minidiab) Glyburide, Glibenclamide
1 to 8 mg/day 2.5 to 40.0 mg/day; dosage >10 mg/day given BID 30 minutes before 1.25 to 20.0 mg/day
meals
initial: 1 to 2 mg once daily, administered Initial, 2.5 to 5 mg orally once
with breakfast or the first main meal. (Immediate-release) Initial, 5 mg orally once daily before breakfast; daily; titrate in increments of no
titration, 2.5- to 5-mg increments; allow several days between titration more than 2.5 mg weekly based on
Titration: If adequate glycemic control is not steps; MAX 40 mg daily (doses above 15 mg should be divided) glycemic response; MAX 5 mg/day
obtained, may increase dose in 1 to 2 mg (Extended-release) Initial, 5 mg orally once daily before breakfast
increments no more frequently than every 1 titrate dose until adequate glycemic control is achieved; MAX 20 mg MAX 20 mg/day
Dose & dose adjustment [2]
to 2 weeks. daily
Maximum: 8 mg/day. Hepatic impairment Hepatic impairment: Initial
The 8 mg/day dosage may be administered in Immediate release: Oral: Initial: 2.5 mg once daily; maintenance dosing and maintenance dosing should be
1 or 2 divided doses should be conservative to avoid hypoglycemia conservative to avoid
Extended release: Oral: Initial: 2.5 mg once daily; maintenance dosing hypoglycemia (consider initiating
should be conservative to avoid hypoglycemia at 1.25 mg/day).
Hepatic Impairment: Renal Impairment: Renal impairment: Avoid use;

no dosage adjustments eGFR ≥50 mL/minute/1.73 m2: No dose adjustment necessary. if use is necessary, initial and
eGFR 10 to <50 mL/minute/1.73 m2: Initial: 2.5 mg once daily. maintenance dosing should be
Renal Impairment: eGFR <10 mL/minute/1.73 m2: Avoid use if possible. If necessary, conservative to avoid
if eGFR <15 mL/minute/1.73 m2: Consider initial dose of 2.5 mg once daily hypoglycemia (consider initiating
alternative therapy Hemodialysis, intermittent (thrice weekly): Not likely to be at 1.25 mg/day).
dialyzable
Dose for eGFR <10 mL/minute, use with caution Dialysis: Avoid use.
Peritoneal dialysis: Dose for eGFR <10 mL/minute, use with caution
 ACE inhibitors, anabolic steroids, androgens, azole antifungals, bromocriptine, chloramphenicol, clarithromycin, disopyramide, fibric acid derivatives,
fluoxetine, guanethidine, H2-receptor antagonists, insulin, magnesium salts, MAO inhibitors, methyldopa, NSAIDs, octreotide, oral anticoagulants,
oxyphenbutazone, phenylbutazone, probenecid, quinidine, quinolones, salicylates, sulfonamides, tetracycline, theophylline, tricyclic antidepressants, urinary
acidifiers: Increased risk of hypoglycemia
 asparaginase, calcium channel blockers, cholestyramine, clonidine, corticosteroids, danazol, diazoxide, estrogen, glucagon, hydantoins, isoniazid, lithium,
morphine, nicotinic acid, oral contraceptives, phenothiazines, rifabutin, rifampin, sympathomimetics, thiazide diuretics, thyroid drugs, urinary alkalinizers:
Increased risk of hyperglycemia
 beta blockers: Possibly hyperglycemia or masking of hypoglycemia signs
 digoxin: Increased risk of digitalis toxicity
pentamidine: Initially hypoglycemia and then hyperglycemia if beta cell damage occurs
CNS: Abnormal gait, anxiety, asthenia, chills, depression, dizziness, Common Common
fatigue, headache, hypertonia, hypoesthesia, Endocrine metabolic: Endocrine metabolic:
malaise, migraine headache, nervousness, paresthesia, somnolence, Hypoglycemia Weight increased
syncope, tremor, vertigo Gastrointestinal: Gastrointestinal:
CV: Arrhythmias, edema, hypertension, vasculitis Constipation, Diarrhea, Flatulence, Nausea Epigastric fullness, Heartburn,
EENT: Blurred vision, conjunctivitis, eye pain, pharyngitis, retinal Neurologic: Nausea
hemorrhage, rhinitis, taste perversion, tinnitus Dizziness, Feeling nervous, Headache,
ENDO: Hypoglycemia Tremor Serious
GI: Anorexia, constipation, diarrhea, elevated liver function test results, Cardiovascular:
epigastric discomfort or fullness, flatulence, heartburn, Serious Cardiovascular event risk,
hunger, nausea, proctocolitis, trace blood in stool, vomiting Gastrointestinal: Mortality
[5]
GU: Darkened urine, decreased libido, dysuria, polyuria Gastrointestinal hemorrhage, Endocrine, metabolic:
HEME: Agranulocytosis, aplastic anemia, eosinophilia, hemolytic Gastrointestinal irritation Hypoglycemia
Adverse reactions
anemia, hepatic porphyria, leukopenia, pancytopenia Hematologic: Hematologic:

MS: Arthralgia, leg cramps, myalgia Hemolytic anemia Hemolytic anemia
RESP: Dyspnea Hepatic:
SKIN: Allergic skin reactions, diaphoresis, eczema, erythema Cholestatic jaundice syndrome
multiforme, exfoliative dermatitis, flushing, jaundice, lichenoid (Rare)
reactions, maculopapular or morbilliform rash, photosensitivity, pruritus,
urticaria
 Diabetes complicated by pregnancy; diabetic coma
contraindicat
 hypersensitivity to glimepiride, sulfonylureas, or sulfonamides

Precautions
ions [5]
 ketoacidosis
 Cardiovascular: Increased cardiovascular mortality has been reported with the sulfonylurea tolbutamide; risk cannot be ruled out with other sulfonylureas
 Endocrine and metabolic: Adrenal or pituitary insufficiency increases risk of hypoglycemia, Glucose 6-phosphate dehydrogenase (G6PD) deficiency can lead
&
to hemolytic anemia
 Encourage patient to carry candy or other  patient should avoid activities requiring coordination until drug  This drug may cause cutaneous
simple sugars to treat mild hypoglycemia. effects are realized, as drug may cause dizziness. hypersensitivity, blurred vision,
 Expect a higher risk of hypoglycemia when giving  This drug may cause cutaneous hypersensitivity, diarrhea, heartburn, or nausea.
glimepiride to a malnourished or debilitated patient nausea, or headache.  Instruct patient to monitor for
or one with renal, hepatic, pituitary, or adrenal  Advise patient to immediately report signs/symptoms of signs/symptoms of hyper- or
insufficiency Stevens-Johnson syndrome (flu-like symptoms, spreading red hypoglycemia and to report
 be aware that hypoglycemia may be more difficult to rash, or skin/mucous membrane blistering). difficulties in glycemic control,
[5]
recognize in patients with autonomic neuropathy, the  Instruct patients to monitor for signs/symptoms of hyper- or especially during times of stress
elderly, and patients taking beta blockers or other hypoglycemia and to report difficulties with glycemic control, caused by infection, fever, trauma,
Patient counseling
sympatholytic agents. especially during times of stress caused by infection, fever, or surgery.
 Monitor blood glucose level closely. trauma, or surgery.  Patient should take tablet with
 If photosensitivity is a problem, instruct  Patient should take tablet 30 min before a meal, preferably breakfast or the first main meal of
patient to avoid direct sunlight and to wear breakfast. the day.
sunscreen.  Poor renal function (glipizide may be a better option than
glyburide or glimepiride because drug or active metabolites are
not renally eliminated)
 Achievement of glycemic control, including meeting HbA1c goal, is indicative of efficacy
[5]
 HbA1c: Twice yearly in patients who are meeting treatment goals; every 3 months in patients whose therapy has changed and/or who are not meeting
glycemic goals; more frequently as clinically warranted
Monitoring
 Blood glucose (self-monitoring): As needed to assist in meeting goals of therapy

 Blood (fasting) and urine glucose: Periodically
 Signs and symptoms of hypoglycemia
 Signs and symptoms of hyperglycemia
6) Thiazolidinediones (TZDs or glitazones)
Mechanism of Action Efficacy
 Decreases insulin resistance by enhancing the sensitivity of insulin-dependent tissues, such as adipose tissue,  Obtain baseline liver function tests (LFTs).
skeletal muscle, and the liver Use w/caution if history of heart failure.
 Reduces glucose output from the liver.  Increased risk of fractures and low bone
 Drug activates peroxisome proliferator-activated receptor-gamma (PPARg) receptors, which modulate mass
transcription of insulin-responsive genes involved in glucose control and lipid metabolism.
 In this way, pioglitazone reduces hyperglycemia, hyperinsulinemia, and hypertriglyceridemia in patients with type
2 diabetes mellitus and insulin resistance.
 However, to work effectively, pioglitazone needs endogenous insulin.
 Unlike sulfonylureas, it doesn’t increase pancreatic insulin secretion.
Pioglitazone (Actos)
Dose & Dose adjustment [2] Adverse Reactions [5] Precautions & Contraindications [5] Drug interactions [5]
15 to 45 mg/day CNS: Headache Contraindicated in: gemfibrozil, rifampin: Possibly altered
Administer without regard to meals CV: Congestive heart failure, edema  Diabetic ketoacidosis glucose control
EENT: Blurred vision, decreased visual  hypersensitivity to pioglitazone ketoconazole: Possibly decreased
Hepatic Impairment: [2] acuity, macular edema, pharyngitis,  New York Heart Association metabolism of pioglitazone
Hepatic impairment prior to initiation: sinusitis, tooth disorders (NYHA) Class III or IV heart oral contraceptives: Possibly
no dosage adjustments, should not be HEME: Decreased hemoglobin level and failure decreased effectiveness of oral
initiated if the patient exhibits active hematocrit  severe hepatic dysfunction contraceptives
liver disease or increased transaminases MS: Fractures, myalgia  type 1 diabetes mellitus
(ALT >2.5 times the upper limit of RESP: Upper respiratory tract infection
normal) at baseline. Other: Weight gain
Hepatic impairment during therapy:
Discontinue therapy if ALT is
persistently >3 times ULN or jaundice
occurs.

No dosage adjustment necessary
Patient counseling [5] Monitoring [5]
 Urge patient to report vision changes promptly and expect to have an eye  Be prepared to monitor liver function test results before therapy begins, every 2
examination by an ophthalmologist regardless of when the last examination months during first year, and annually thereafter, as ordered, because drug is
occurred. extensively metabolized in the liver.
 Instruct patient to keep appointments for liver function tests, as ordered,  Expect to stop drug if jaundice develops or ALT values exceed 2.5 times normal.
typically every 2 months during first year of therapy and annually  WARNING Monitor patient for signs and symptoms of congestive heart failure—such
thereafter. as shortness of breath, rapid weight gain, or edema—because pioglitazone can cause
 Inform female patient who uses oral contraceptives that drug decreases fluid retention that may lead to or worsen heart failure.
their effectiveness; suggest that she use another method of contraception  Notify prescriber immediately of any deterioration in the patient’s cardiac status, and
while taking pioglitazone. expect to discontinue the drug, as ordered.
 Also inform female patient that she may be at risk for fractures during  Assess for signs and symptoms of hypoglycemia, especially if patient is also taking
pioglitazone therapy, and urge her to take safety precautions to prevent another antidiabetic drug.
falls and other injuries.  Monitor glycosylated hemoglobin level to assess drug’s long-term effectiveness.
Combination therapy
Ertugliflozin/metformin SGLT2 inhibitor and biguanide: 2.5 to 7.5 mg/500 to Empagliflozin/linagliptin (Glyxambi) 10 to 25 mg/5 mg, 1 tab q am
hydrochloride (Segluromet) 1,000 mg
Canagliflozin/metformin 50 to 150/500 to 1,000 mg, max dose 300/2,000 mg, Alogliptin/pioglitazone (Oseni) 12.5 to 25/15 to 45 mg, max dose
(Invokamet) XR form available 25/45 mg daily
Dapagliflozin/metformin 5 to 10/500 to 1,000 mg, max dose 10/2,000 mg; XR Combination Duetact pioglitazone 1 tab q am
(Xigduo) form available with glimepiride (Duetact): 30/2 to 4
mg,
Empagliflozin/metformin 5.0 to 12.5/500 to 1,000 mg, max dose 25/2,000 mg; Insulin glargine/lixisenatide (Soliqua 15 to 60 units SC qd
(Synjardy) XR form available 100/33)
Glipizide/metformin 2.5/250 mg, 2.5/500 mg, 5/500 mg; 1 to 2 tabs PO qd Insulin degludec/liraglutide 16 to 50 units SC qd
(Metaglip) BID (Xultophy 100/3.6)
Glyburide/metformin 1.25/250 mg, 2.5/5000 mg, 5/500 mg; 1 TO 2 tabs PO Linagliptin/metformin (Jentadueto) 2.5/500 to 1,000 mg, 1 tab PO
(Glucovance) BID BID, max dose 5/2,000 mg
Pioglitazone/metformin available in IR and XR forms Kombiglyze XR—2.5 to 5.0/500 to 1 to 2 tabs PO qd, max dose
(ACTOplus met) 1,000 mg 5/2,000 mg PO daily
Repaglinide/metformin 1/500 mg, 2/500 mg, individualize dose PO BID to Sitagliptin/metformin (Janumet) available in XR
(Prandimet) TID
Complications with Diabetic Mellitus
Cardiovascular Disease and Risk Management
 All hypertensive patients with diabetes should monitor their blood pressure at home
 For individuals with diabetes and hypertension at higher cardiovascular risk (existing atherosclerotic cardiovascular disease [ASCVD] or 10-year ASCVD risk
≥15%), a blood pressure target of, 130/80 mmHg
 For individuals with diabetes and hypertension at lower risk for cardiovascular disease (10-year atherosclerotic cardiovascular disease risk <15%), treat to a blood
pressure target of <140/90 mmHg
 ACE inhibitors or angiotensin receptor blockers are recommended first-line therapy for hypertension in people with diabetes and coronary artery disease.
 For patients treated with an ACE inhibitor, angiotensin receptor blocker, or diuretic, serum creatinine/estimated glomerular filtration rate and serum potassium
levels should be monitored at least annually
Lipid Management—Lifestyle Intervention

 Reduction of saturated fat and trans fat; increase of dietary n-3 fatty acids, viscous fiber, and
plant stanols/sterols intake; and increased physical activity should be recommended to
improve the lipid profile and reduce the risk of developing atherosclerotic cardiovascular
disease in patients with diabetes
 Target: TG goal: < 150 mg/dl & HDL-c goal: > 40 mg/dl for men, > 50 mg/dl for women,
LDL-C < 100 mg/Dl, < 70 mg/dL an option in those with existing cardiovascular
disease
 For patients with diabetes aged 40–75 years without atherosclerotic cardiovascular disease,
use moderate-intensity statin therapy in addition to lifestyle therapy.
 For patients with diabetes aged 20–39 years with additional atherosclerotic cardiovascular
disease risk factors, it may be reasonable to initiate statin therapy in addition to lifestyle
therapy.
 In patients with diabetes at higher risk, especially those with multiple atherosclerotic
cardiovascular disease risk factors or aged 50–70 years, it is reasonable to use high-intensity statin therapy.
 In adults with diabetes and 10-year ascvd risk of 20% or higher, it may be reasonable to add ezetimibe to maximally tolerated statin therapy to reduce ldl cholesterol
levels by 50% or more.
Antiplatelet Agents
 Use aspirin therapy (75–162 mg/day) as a secondary prevention strategy in those with diabetes and a history of atherosclerotic cardiovascular disease.
 For patients with atherosclerotic cardiovascular disease and documented aspirin allergy, clopidogrel (75 mg/day) should be used.
 Dual antiplatelet therapy (with low-dose aspirin and a P2Y12 inhibitor) is reasonable for a year after an acute coronary syndrome and may have benefits beyond this
period.
 Long-term treatment with dual antiplatelet therapy should be considered for patients with prior coronary intervention, high ischemic risk, and low bleeding risk to
prevent major adverse cardiovascular events.
 Combination therapy with aspirin plus low-dose rivaroxaban should be considered for patients with stable coronary and/or peripheral artery disease and low
bleeding risk to prevent major adverse limb and cardiovascular events.
 Aspirin therapy (75–162 mg/day) may be considered as a primary prevention strategy in those with diabetes who are at increased cardiovascular risk, after a
comprehensive discussion with the patient on the benefits versus the comparable increased risk of bleeding
 In patients with type 2 diabetes and established atherosclerotic cardiovascular disease, multiple atherosclerotic cardiovascular disease risk factors, or diabetic
kidney disease, a sodium–glucose cotransporter 2 inhibitor with demonstrated cardiovascular benefit is recommended to reduce the risk of major adverse
cardiovascular events and/or heart failure hospitalization.
 In patients with type 2 diabetes and established atherosclerotic cardiovascular disease or multiple risk factors for atherosclerotic cardiovascular disease, a
glucagon-like peptide 1 receptor agonist with demonstrated cardiovascular benefit is recommended to reduce the risk of major adverse cardiovascular events.
 In patients with type 2 diabetes and established heart failure with reduced ejection fraction, a sodium–glucose cotransporter 2 inhibitor with proven benefit in
this patient population is recommended to reduce risk of worsening heart failure and cardiovascular death.
 In patients with known atherosclerotic cardiovascular disease, particularly coronary artery disease, ACE inhibitor or angiotensin receptor blocker therapy is
recommended to reduce the risk of cardiovascular events.
 In patients with prior myocardial infarction, b-blockers should be continued for 3 years after the event
Diabetic Retinopathy
 If there is no evidence of retinopathy for one or more annual eye exams and glycemia is well controlled, then screening every 1–2 years may be considered.
 If any level of diabetic retinopathy is present, subsequent dilated retinal examinations should be repeated at least annually by an ophthalmologist or optometrist.
 If retinopathy is progressing or sight-threatening, then examinations will be required more frequently
 The presence of retinopathy is not a contraindication to aspirin therapy for cardioprotection, as aspirin does not increase the risk of retinal hemorrhage.
Chronic Kidney Disease
 For patients with type 2 diabetes and diabetic kidney disease, consider use of a sodium–glucose cotransporter 2 inhibitor in patients with an estimated glomerular
filtration rate ≥30 mL/min/1.73 m2 and urinary albumin >300 mg/g creatinine.
 In patients with type 2 diabetes and diabetic kidney disease, consider use of sodium–glucose cotransporter 2 inhibitors additionally for cardiovascular risk
reduction when estimated glomerular filtration rate and urinary albumin creatinine are >30 mL/min/1.73 m2 or.300 mg/g, respectively
 In patients with chronic kidney disease who are at increased risk for cardiovascular events, use of a glucagon-like peptide 1 receptor agonist reduces renal end
point, primarily albuminuria, progression of albuminuria, and cardiovascular events
 For people with no dialysis dependent chronic kidney disease, dietary protein intake should be approximately 0.8 g/kg body weight per day (the recommended daily
allowance).
 For patients on dialysis, higher levels of dietary protein intake should be considered, since malnutrition is a major problem in some dialysis patients.
 In non-pregnant patients with diabetes and hypertension, either an ACE inhibitor or an angiotensin receptor blocker is recommended for those with modestly
elevated urinary albumin-to-creatinine ratio (30–299 mg/g creatinine) B and is strongly recommended for those with urinary albumin-to-creatinine ratio ≥300mg/g
creatinine and/or estimated glomerular filtration rate <60 mL/min/1.73 m2.
 An ACE inhibitor or an angiotensin receptor blocker is not recommended for the primary prevention of chronic kidney disease in patients with diabetes who
have normal blood pressure, normal urinary albumin-to-creatinine ratio (<30 mg/g creatinine), and normal estimated glomerular filtration rate.
Neuropathy
 Optimize glucose control to prevent or delay the development of neuropathy in patients with type 1 diabetes A and to slow the progression of neuropathy in patients
with type 2 diabetes.
 Assess and treat patients to reduce pain related to diabetic peripheral neuropathy B and symptoms of autonomic neuropathy and to improve quality of life.
 Pregabalin, duloxetine, or gabapentin are recommended as initial pharmacologic treatments for neuropathic pain in diabetes
Foot Care
 Perform a comprehensive foot evaluation at least annually to identify risk factors for ulcers and amputations
 The risk of ulcers or amputations is increased in people who have the following risk factors:
 Poor glycemic control, Peripheral neuropathy with LOPS, Cigarette smoking, Foot deformities, Pre-ulcerative callus or corn
 History of foot ulcer, Amputation, Visual impairment, CKD (especially patients on dialysis)

Diabetis 2

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Diabetis 2

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‫‪Diabetes Mellitus Type 2 Management‬‬

‫مديرية الشئون الصحية بالقليوبية‬

‫‪Diabetes Mellitus Type 2 Management‬‬

‫قسم الصيدلة اإلكلينيكية‬

GENERAL PREVENTION [1]

PHARMACOLOGIC THERAPY FOR TYPE 2 DIABETES [1]

Concerns related to adverse effects:

Renal Impairment: [2] Hepatic Impairment: [2] Hepatic Impairment: qd

warfarin: Possibly increased INR with increased risk of bleeding

Usually, no dosage adjustment is needed for a patient taking metformin.

box warning) type 2 because drug may patients with multiple

 Hypersensitivity to exenatide or its syndrome type 2

components  Use liraglutide cautiously in patients with a

until the dial has returned to 0 and for an

 less expensive and better tolerated than

thyroid cancer and need to report any

pancreatitis, such as persistent, severe dyspnea, or persistent hoarseness.

Canagliflozin (Invokana) Dapagliflozin (Farxiga) Empagliflozin (Jardiance)

 Cardiovascular disease (risk of hypotension).

 monitor for genital mycotic infections and UTI;

4) Dipeptidyl peptidase-4 inhibitors

Sitagliptin (Januvia) Saxagliptin (Onglyza) Vildagliptin (Vildagluse) Linagliptin Alogliptin (Nesina)

 If present, notify prescriber and expect to be discontinue.

>2.5 x ULN; discontinue use in

patients who develop ALT or

effects  atazanavir, clarithromycin, Possibly increased reduced).

Role in Blood Sugar Management Duration Peak Onset Brand Names

Patient counseling [5] Monitoring [5]

Acarbose (Precose) Miglitol (Glyset)

Renal Impairment: [2]

hormones: Possibly decreased therapeutic effects of acarbose

ileus, jaundice SKIN: Rash (transient)

 history of bowel obstruction  hypersensitivity to miglitol

 hypoglycemia reach small intestine.

 evaluate glucose control and patient compliance. glucose control.

Hepatic Impairment: [2] Hepatic Impairment: [2]

Renal Impairment: [2] Renal Impairment: [2]

 Concurrent therapy with gemfibrozil  Diabetic ketoacidosis

 diabetic ketoacidosis  hypersensitivity to nateglinide

salicylates, sulfonamides: Enhanced hypoglycemic effects

insulin because the combination may increase the risk of

Hepatic Impairment: Renal Impairment: Renal impairment: Avoid use;

anemia, hepatic porphyria, leukopenia, pancytopenia Hematologic: Hematologic:

 hypersensitivity to glimepiride, sulfonylureas, or sulfonamides

 Blood glucose (self-monitoring): As needed to assist in meeting goals of therapy

Renal Impairment: [2]

Lipid Management—Lifestyle Intervention

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