Goodman &Gilman's: The Pharmacological Basis of Therapeutics, 13e >Endocrine Pancreas and

Pharmacotherapy of Diabetes Mellitus and Hypoglycemia

Laurence L. Brunton, Randa Hilal-Dandan, Björn C. Knollmann+
Table 47–7Comparison of Agents Used for Treatment of Diabetes

AGENT-SPECIFIC AGENT-SPECIFIC CONTRAINDICATIONS AND

TYPE Agent MECHANISM OF ACTION HbA1C REDUCTION (%)a
ADVANTAGES DISADVANTAGES PRECAUTIONS

Oral

GFR <50 mL/min, CHF,

Weight neutral, do not cause Diarrhea, nausea, lactic
Biguanidesc ↓ Hepatic glucose production 1–2 radiographic contrast studies,
hypoglycemia, inexpensive acidosis
seriously ill patients, acidosis

Dipeptidyl peptidase 4 Prolong endogenous GLP-1

0.5–0.8 Do not cause hypoglycemia Expensive ↓ Dose with renal disease
inhibitorsc action

GI flatulence, liver function

α-Glucosidase inhibitorsc ↓ GI glucose absorption 0.5–0.8 ↓ Postprandial glycemia Renal/liver disease
tests

Insulin
↑ Insulin secretion 1–2 Inexpensive Hypoglycemia, weight gain Renal/liver disease
secretagogues—sulfonylureasc

Insulin
Rapid onset of action, lower Hypoglycemia, precautions for
secretagogues—nonsulfonylur ↑ Insulin secretion 1–2 Renal/liver disease
easc postprandial glucose elderly and renal impairment

Mild weight loss and BP ↑ Rate of lower urinary tract

SGLT2 inhibitorsc (the reduction; do not cause and genital mycotic infections;
↑ Renal glucose excretion 0.9–1.2 Renal disease
gliflozins) hypoglycemia; CV benefit hypotension; rarely DKA; see
(empagliflozin, canagliflozin) text for canagliflozin

Peripheral edema, CHF, weight

Thiazolidinedionesc (the ↓ Insulin resistance, ↑ glucose
0.5–1.4 Lower insulin requirements gain, fractures in females, CHF, liver disease
glitazones) utilization
macular edema

Parenteral

↑ Glucose utilization, ↓ hepatic Well-known safety/adverse

Injection, weight gain,
Insulin glucose production, and other Not limited effect profile from much clinical Hypoglycemia
hypoglycemia
anabolic actions experience

Injection, nausea, ↑ risk of Renal disease, agents that also

↑ Insulin, ↓ glucagon, slow Weight loss, CV benefit
GLP-1R agonistsc 0.5–1.5 hypoglycemia with insulin slow GI motility, pancreatitis,
gastric emptying, satiety (liraglutide)
secretagogues medullary carcinoma of thyroid

Slow gastric emptying, ↓ Reduce postprandial glycemia; Injection, nausea, ↑ risk of Agents that also slow GI
Amylin agonistsb,c 0.25–0.5
glucagon weight loss hypoglycemia with insulin motility

Other

Medical nutrition therapy and ↓ Insulin resistance, ↑ insulin Weight loss, improved CV Compliance difficult, long-term
1–3
physical activityc secretion health success low

↑ Glucose utilization, ↓ hepatic

Inhaled insulinc,d glucose production, other 0.25–0.5 Rapid onset of action Limited clinical experience Pulmonary disease, smoking
anabolic actions