Non Insulin Management Of

DM
Done By: Dr. Muhannad AlSahli.
Supervisor: Dr.Fahad AlBedawi.
:OBJECTIVES

.ORAL MEDICATION FOR DM

.GUIDELINE FOR TREATMENT

.TREATMENT ACCORDING TO DISEASE STATUS

2
4
 Alpha-glucosid
Sensitizers Secretagogues Peptide analogs Glycosuri ase inhibitors
cs

Glucagon-like
peptide analogs
Biguanides and agonists SGL2-Inhibit
or
Thiazolidine- Dipeptidyl
Peptidase-4
diones Inhibitors

Sulfonylure
as

Meglitinide
s
Biguanides ( Metformin )
.Insulin Sensetizer *

.Decrease hepatic glucose production -1

.Decrease gastrointestinal glucose absorption -2
.Increase target cell insulin sensitivity -3

.Should be the 1st choice unless there are contraindications -

.Continue if adding other medications-
*

A1C reduction Disadvantages Advantages

to 2% 1.5% Diarrhea , Abdominal .No Hypoglycemia
Pain, muscle pain or No wt gain
.weakness Modest TG reduction
.Lactic acidosis(rare) Reduce incidence of
dementia
ASCVD Benefit
 METFORMIN REDUCE
CVD IN DM2

COMPLICATION RR% (P VALUE

S )
Any related Dm End 32 (P = 0.002)
point %
DM -related death 42 (P = 0.017)
%
All-cause mortality 36 (P = 0.011)
%
MI 36 (P = 0.01)
UKPDS 34. Effect of intensive blood-glucose control with)
%
metformin on complications in overweight patients with type 2
diabetes Lancet. 1998; 352: 854-865
 METFORMIN
USE IN CKD

eGFR Recommendation RFT monitoring

(ml/min)
60 ≤ No CI Annually /when
indicated
30 ≤ - 45 > Prescribe with ✓ Close monitoring
45 ≤ - 60 > Can be used Every 3-6 m
caution Q3 m
Reduce dose ✓
50%
Don’t start new ✓
pt
30> Stop metformin
 Cont. (Metformin)

: Caution-

.Must check creatinine prior to use -1

. Stopped if Serum creatinine level ≥1.5 mg/dL in M or ≥1.4 mg/dL in F -2
.Discontenue if GFR < 30 mL/min -3
.Temporary stopped with radiologic contrast study within 48 hours -4
.Check for B12 deficiency periodically -5

.Take metformin with a meal

Thiazolidinediones
(Pioglitazone ◘ – Rosiglitazone )

.Insulin Sensitizer *

.Increase insulin receptor sensitivity -

.Increase hepatic glucose uptake -

A1C reduction Disadvantages Advantages

Weight ↑- No-
Edema/heart failure- hypoglycemia
to 1.4% 0.5% . Bone fractures , ↑ LDL-C- Triglycerides ↓-
Risk of pancreatic, bladder,↑- HDL-C ↑-
.prostate CA

:Contraindications
. NYHA class III/IV heart failure
 Secretagogu
es

Drugs that increase

insulin output from
Sulfonylure .the pancreas Meglitinide
as s

Glipizide (glucotrol) - ✔ Repaglinide (Starlix) -

Gliclazide (diamicron)-✔ Nateglinide (Prandin) -
Glibenclamide -
Glyburide -
Sulfonylureas
(Glipizide , Gliclazide ◘ ,Glibenclamide ◘ , Glyburide)

.Simulate beta-cell to release insulin

A1C reduction Disadvantages Advantages

to 1.2% 0.4% Hypoglycemia CHF Can be used in OSA ,
Weight ↑

.Accepted in mild renal dysfunction except Glyburide

.Administer with meal
Meglitinides
(Repaglinide , Nateglinide)

. Stimulate release of insulin from the pancrease

.Rapid acting ( half life < 1hr)

A1C reduction Disadvantages Advantages

Hypoglycemia Postprandial glucose ↓
Weight ↑ Dosing flexibility
to 1.0% 0.5% Frequent dosing Can used in RF or
schedule .Cardiopulmonary disorder

Taken with or shortly before meals to boost the insulin response to each
.meal
.If a meal is skipped, the medication is also skipped
 Peptide
analogs

GLP-1 DPP-4
receptor inhibitors
agonists
Exenatide
Sitagliptin (Januvia) ✔
Liraglutide ® ✔
Vildagliptin
Albiglutide
Linagliptin (Tradjenta)
Lixisenatide
Alogliptin (Nesina)
Dulaglutide
Glucagon-like peptide analogs and agonists
(Exenatide ,® Liraglutide, Albiglutide , Lixisenatide , Dulaglutide)

New group of injectable drugs for treatment of type 2 diabetes

.Stimulating the release of insulin by the pancreas after eating -
Suppress postprandial glucagon secretion -
Slow gastric emptying -
Liraglutide : Consider in patient with cardiovascular ®
Liraglutide (FDA Approved for prevention of non fatal MI, non fatal stroke, CV death (
in dm2 with established CVD 22%)
.disease to reduce the mortality
C.I: Personal or family history of MTC

A1C reduction Disadvantages Advantages

GI symptoms No hypoglycemia -
to 2.0% 0.8% Heart rate ↑ Weight ( 1 - 4 kg is likely ) ↓-
Injectable
Pancreatitis
Dipeptidyl Peptidase-4 Inhibitors
(Sitagliptin, Vildagliptin , Linagliptin ◘, Alogliptin)

.Block DPP4 (enzyme that breaks down natural incretins) -

.Insulin secretion ↑ -

A1C reduction Disadvantages Advantages

Angioedema/urticaria .No hypoglycemia -
to 0.9% 0.5% Acute pancreatitis Linagliptin not renally excreted -
Heart failure ↑ ( good choice in elderly)
 Glycosuri
cs

SGL2-Inhibitor

Canagliflozin (Invokana)
Dapagliflozin (Fargixa)
Empagliflozin ✔
SGL2-Inhibitor
(Canagliflozin ,Dapagliflozin , Empagliflozin)

.Block reabsorption of glucose in the kidney –

.Increase urinary excretion of glucose –
A1C reduction Disadvantages Advantages
.Genitourinary infections ↑ No hypoglycemia
Polyuria Weight (0.7 – 3.5 kg is Typical ) ↓
to 0.9% 0.5% .Hypotension BP ↓
LDL-C ↑
Creatinine ↑
.Renal Insufficiency required adjustment dosage
. Empagliflozin : Consider in patient with cardiovascular disease to reduce the mortality ®
ITS FDA approved to dec CV mortality (38%) reduce hospitalization 35%

Canagliflozin : FDA approved to Dec MACE ®

Both show dec in CKD progression

,
Alpha-glucosidase inhibitors

Miglitol (Glyset) -
Acarbose (Precose) - ✔
α-Glucosidase inhibitors
(Miglitol , Acarbose)

. Delay intestinal carbohydrate digestion and absorption

A1C reduction Disadvantages Advantages

Gastrointestinal side effects - No hypoglycemia
to 0.8% 0.5% .Postprandial glucose ↓
Cardiovascular events↓

: Caution
. Avoid when creatinin < 25 ml / min
. Avoid in cirrhosis , inflammatory bowel disease
American Diabetic Association Guidelines 2020

Always Metformin (if cannot any)+ life-style for all the next •
step
A. Established ASCVD/ CKD
Mainly (HF/ CKD)= SGLT2 (if eGFR <45/ CI/ not tolerated > •
GLP1): avoid
pioglitazone in HF
Mainly ASCVD: GLP1/ SGLT2 •
:B. No Established ASCVD/ CKD
Obesity: Preferably use GLP1/ SGLT2 > DPP4 •
Risk Hypoglycaemia: Preferably use GLP1/ DPP4/SGLT2/TZD •
Cost issue: Preferably use SU/ TZD > Insulin •
29
30
 Group Common Hypoglycemia CKD Side Mechanism of Notes
Examples .& Wt Effects Action

Biguanides Metformin Neutral on eGFR • GI upset (less with • Increase insulin • ”Acidosis Temporary withdraw= “ Lactic •
Insulin gradual increase to sensitivity Reduce Acute heart failure, hepatic •
(Glucophage) Hypos and <45= half
Sensitizers weight dose
max dose/MR)
Interfere with
•
absorption &
hepatic
failure or Acute renal
failure & Before
eGFR<30= • B12 production GA/Contrast
stop absorption Proven CV Benefits •

=TZDs Pioglitazone Hypos rare, No need • Fluid • Increase • CI past h/o bladder ca or •
to adjust retention hematuria
Glitazones (Actos) but weight Insulin
dose Increase risk • CI: CCF, hepatic failure •
gain of fractures sensitivity CI Fractures •

Insulin Sulphonylurea Glibenclamide Hypos and Avoid • GI • Stimulate •

(Glyburide= Diatab)- long upset Insulin
Secretagogues weight gain
long acting Gliclazide acting secretion
(Diamicron) Glipizide (slow)
Glimepride (Amaryl)
Tolbutamide= long
acting

Glinides Repaglinide No need • Rash and • Quick stimulate • CI hepatic

(Novonorm) to adjust Urticaria Insulin secretion impairment
Nateglinide (Starlix) dose GI upset •
DPP4-Inhibi Sitagliptin Neutral on Linagliptin=sa • Risk of • More Insulin •
Incretins (Januvia) weight and fe, reduce pancreatitis Secretion
tors
Vildagliptin rarely hypos dose others Reduce glucagon •
(Galvus) and hepatic
Linagliptin glucose
(Trajenta) production
Saxagliptin(Onglyza
Exenatide (Byetta) bid
) Alogliptin Weight loss Avoid • Risk • CI in Medullary thyroid
GLP1-Ago
Liraglutide (Victoza)/day and rarely if pancreatitis cancer
nist Lixisenatide (Lyxumia)/d hypos eGFR< GI •
Albiglutide/ weeks 30 disturbances
.Dulaglutide (Trulicity)/ wk

SGLT2 Dapagliftozin (Forxiga) Weight loss Not • UTI • Sodium-Glucose • Reduce BP

Empagliflozin and rarely effective if DKA with slight • transporter 2 Possible CV and renal
inhibitor=
(Jardiance) hypos (eGFR<60) elevation Inhibitors benefits
Gliflozins Canagliflozin (Invokana) glucose increase glucose
(<14mmol) .excretion in urine

Alfa-glucosi Acarbos diarrhoea, • Inhibitor intestinal •

e flatulence and alpha glucosidase=
dase
pain delay absorption
inhibitors complex carbs:
starch and sucrose
: Reference
33