Table 3.

Oral antidiabetic drugs: pros and cons in older adults

Antidiabetic drug	Mechanism of action	Effect on decreasing HbA1c	Pros (benefits) in older adults	Cons (side effects in older adults	Practical tips
Metformin	Decreases gluconeogenesis and increases glycogenolysis	1%–2%	No hypoglycemia No weight gain Low cost Positive effect on lipids Decreases macrovascular complications	Lactic acidosis in severe CKD GI symptoms	Take on full stomach Start low dose to minimize GI side effects and titrate up slowly Cautiously in older adults with increased risk of lactic acidosis
Insulin secretagogues (SUs and glinides)	Stimulates insulin secretion by inducing a B-cell interaction with a SU receptor	0.5%–1.0%	Once a day Works fast	Hypoglycemia	Non preferred in older adults because of the risk of hypoglycemia
Alpha glucosidase inhibitors	Slow carbohydrate absorption by blocking alpha glycosidase and increase GLP-1 level	0.5%–1.0%	Improves postprandial BG	GI symptoms	To be taken with first bite of food
Thiazolidinedione	PPARγ agonist and regulate carbohydrate and lipid metabolism, enhance tissue response to insulin	0.9%–1.5%	No hypoglycemia when used as monotherapy	Slow onset of action HF Fluid retention	Don’t use if patient has osteoporosis or macular degeneration, which are common in older adults.
DPP-4 inhibitors	Stimulates insulin secretion and inhibits glucagon secretion by increasing endogenous GLP-1	1%	No hypoglycemia when used as monotherapy	Risk of hypoglycemia if used with SU	Well-tolerated and low risk of hypoglycemia Can be used even in the presence of CKD Avoid if there is history of pancreatitis.
GLP-1 receptor agonists	Stimulate insulin secretion, inhibit hepatic glucose and delay gastric emptying	1%	Cardiac (IHD) and renal protective	GI symptoms	Once a week or daily formulations Start with lowest dose possible and titrate up. May cause weight loss Avoid if there is history of pancreatitis or medullary thyroid carcinoma or MEN.
SGLT-2i	Prevent glucose reabsorption in the nephron and increase glucose excretion in the urine by inhibiting the SGLT-2 protein	1%	HF and renal protection Low risk of hypoglycemia Can be used in diabetes of any duration	Dehydration GU infections DKA	Recommended for patients with diabetes and HF and/or renal disease Monitor for cystitis and yeast infections. Keep up with oral hydration to volume depletion Avoid in patients with T1DM.

BG, blood glucose; CKD, chronic kidney disease; DKA, diabetic ketoacidosis; DPP-4, dipeptidyl peptidase-4; GI, gastrointestinal; GLP-1, glucagon-like peptide-1; HbA1c, glycated hemoglobin; HF, heart failure; IHD, ischemic heart disease; MEN, multiple endocrine neoplasia; PPARγ, peroxisome proliferator-activated receptor; SGLT-2i, sodium–glucose cotransport 2 inhibitor; SU, sulfonylurea; T1DM, type 1 diabetes mellitus.