Background: The vast majority of individuals diagnosed with diabetes are low/middle income
and may have access to only three of the 11 oral hypoglycemic medications (OHMs) due to cost:
metformin intermediate release (IR) or extended release (ER), sulfonylureas (glimepiride, glipizide,
glyburide), and pioglitazone. Sulfonylureas and pioglitazone have had significant controversy related to
potential adverse events, but it remains unclear whether these negative outcomes are class, drug, or
Objective: We conducted a narrative review of low-cost OHMs.
Methods: We evaluated the maximum recommended (MAX) compared to the most effective (EFF)
daily dose, time-to-peak change in HbA1c levels, and adverse events of low-cost oral hypoglycemic
Results: We found that the MAX was often greater than the EFF: metformin IR/ER (MAX: 2,550/2,000
mg, EFF: 1,500–2,000/1,500–2,000 mg), glipizide IR/ER (MAX: 40/20 mg, EFF: 20/5 mg), glyburide
(MAX: 20 mg, EFF: 2.5–5.0 mg), pioglitazone (MAX: 45 mg, EFF: 45 mg). Time-to-peak change in
HbA1c levels occurred at weeks 12–20 (sulfonylureas), 25–39 (metformin), and 25 (pioglitazone).
Glimepiride was not associated with weight gain, hypoglycemia, or negative cardiovascular events relative
to other sulfonylureas. Cardiovascular event rates did not increase with lower glyburide doses
(p<0.05). Glimepiride and pioglitazone have been successfully used in renal impairment.
Conclusion: Metformin, glimepiride, and pioglitazone are safe and efficacious OHMs. Prescribing at
the EFF rather than the MAX may avoid negative dose-related outcomes. OHMs should be evaluated as
individual drugs, not generalized as a class, due to different dosing and adverse-event profiles; Glimepiride
is the preferred sulfonylurea since it is not associated with the adverse events as others in its class.