Table 1.

Pharmacological agents for glycemic control.

Class of antidiabetic medication (route of administration)	Representative agents	Mechanism of action	T1/2 and metabolism	HbA1C reduction (%)	Risk of hypoglycemia	Effect on body weight	Metabolic alterations	Cardiovascular (CV) benefit and risk	Other adverse effects/additional comments
Biguanide (o)	Metformin	Insulin sensitizer Numerous effects on inhibition of hepatic glucose production	5 h; unmetabolized, renal excretion	1–2	None	Mild weight loss due to anorectic effect	Lactic acidosis (very rare) May cause nausea/vomiting or diarrhea after introduction, which may result in electrolyte or pH alterations	Reduce MI by 39% and coronary deaths by 50% (UKPDS)	Vitamin B12 deficiency, which may cause anemia and neuropathy (risk in elderly) Very safe drug, but stop metformin if creatinine >1.5 mg/dL in males and >1.4 mg/dL in females
Dipeptidyl peptidase 4 (DPP-IV) inhibitor (o)	Sitagliptin Saxagliptin Vidagliptin Linagliptin Alogliptin	Inhibition of degradation of GLP	Excreted by kidneys (except linagliptin) (needs dose reduction in renal failure)	0.5–0.8	Low			Long-term trials to assess CV risk; decreases postprandial lipemia, however, may cause CHF by degradation of BNP	Pancreatitis Upper RTI infection
Sodium-glucose cotransporter (SGLT2) inhibitor (o)	Canagliflozin Dapagliflozin Empagliflozin	Glucosuria due to blocking (90%) of glucose reabsorption in renal PCT; insulin-independent mechanism of action			Low			Positive CV effect due to reduction of sodium and uric acid absorption and reduction of BP	Ketoacidosis (rare) Genital mycosis May increase LDLc Bone fractures
Insulin (p)	Short-acting Regular (R) (Humulin R, Novolin R) Intermediate NPH (N) Long-acting Insulin glargine (Lantus) Insulin detemir (Levemir) Insulin degludec (Tresiba) Rapid-acting Humalog (Lispro) Novolog (Aspart) Glulisine (Apidra) Pre-mixed 75% insulin lispro protamine/25% insulin lispro (Humalog Mix 75/25) 50% insulin lispro protamine/50% insulin lispro (Humalog Mix 50/50) 70% insulin lispro protamine/30% insulin aspart (Novolog 70/30) 70% NPH insulin/30% regular	Activation of insulin receptors and downstream signaling in multiple sensitive tissues	30 min-1 r (onset of action) Peak 2–5 h Duration of action 8 h 1.5–4 h (onset of action) Peak 4–12 h Duration of action 24 h 0.8–4 h (onset of action) Peak minimal Duration of action 24 h 10–30 min (onset of action) Peak 30 min–3 h Duration of action 3–5 h 5–15 min (onset of action) Peak dual Duration of action 10–16 h 30–60 min (onset of action) Peak dual Duration of action 10–16 h	1–2.5	Prominent	Weight gain		HF if used in combination with thiazolidinediones (TZD)	Lipoatrophy and lipohypertrophy at sites of injection Allergy to injection components Levemir Food and Drug Administration -approved for gestational diabetes mellitus
GLP-1 agonists (p)	Liraglutide Exenatide Dulaglutide	Activate GLP1 receptor Increased insulin secretion, decreased glucagon, delayed gastric emptying, increased satiety	24 h 4–6 h (short acting) 7 days (long acting, extended release) 7 days	0.5–1.5	No [risk if used in combination with sulfonylureas (SU)]	Weight loss		Reduce CV risk	Nausea, vomiting, pancreatitis, C cell tumor of thyroid (contraindicated in MEN type 2)
SU (o)	Glimepiride Glipizide Glyburide	Insulin secretion		1–2	Prominent (severe in renal failure)	Weight gain		Increased cardiovascular disease risk, mainly due to hypoglycemia	Use beta-blockers with caution
TZD (o)	Rosiglitazone Pioglitazone	True insulin sensitizer		0.5–1.4		Weight gain		Cardiac failure, pedal edema	Bladder cancer; fractures

O, oral; p, parenteral; iv, intravenous; sc, subcutaneous.