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Drug History
PD was started on metformin, and although it was well-tolerated with increasing doses up to 1000 mg BID, after 4 months, her HbA1c was reduced by only 0.3%, and the metformin was discontinued. Glimepiride, a sulfonylurea, was substituted at 2 mg/d. On this dose, she developed hypoglycemia while exercising, and the dose was lowered to 1 mg/d. Her HbA1c was maintained between 7.0% and 7.2% for several years. PD was able to lose weight to an acceptable level, which stayed in the range of 175–180 (BMI 25–26). Gradually, the dose of glimepiride was increased to 4 mg/d.
Q: What explains PD’s lack of response to metformin?
A: Type 2 diabetes mellitus is the result of a triad of abnormalities: excessive hepatic glucose production, peripheral resistance to insulin action principally in skeletal muscle tissue, and impaired pancreatic insulin secretion. In less obese patients with Type 2 diabetes, impaired insulin secretion may be more predominant, as insulin resistance tends to be more severe in subjects with obesity, especially when abdominal in distribution. Metformin inhibits hepatic glucose production and increases insulin utilization, but only in the presence of adequate amounts of insulin. Metformin is known to be more effective in obese patients with insulin resistance for this reason.1 Note also that this patient had a history of gestational diabetes, a condition that occurs in pregnancy. Gestational diabetes is well-known to be associated with insulin deficiency because of insufficient pancreatic insulin secretion.2
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