Metformin and glimepiride with basal insulin lowered HbA1c the most
Key takeaway:
In adults with uncontrolled type 2 diabetes, continuing both metformin and glimepiride when starting insulin glargine lowered HbA1c more than pairing glargine with either drug alone over 24 weeks.
Study at a glance
What was studied
Which oral add-on regimen works best with insulin glargine in uncontrolled type 2 diabetes
Study type
Randomized Controlled Trials (RCTs)
duration
Medium-Term (3–12 mo)
Intervention
Metformin, Glimepiride, Metformin + glimepiride
Outcomes
HbA1c, Fasting Plasma Glucose, Hypoglycemia events, Daily insulin dose
Funding
Industry sponsored
Main effects
HbA1c ↓ most with insulin glargine plus metformin and glimepiride
Fasting plasma glucose ↓ in all three treatment groups
HbA1c ≤7.5% ↑ more often with triple therapy
Hypoglycemia ↔ stayed broadly similar across groups
Evidence Summary
| Intervention | Outcome | Measured Change | Study Effect |
|---|---|---|---|
 Glimepiride (Medications) |  Fasting Plasma Glucose (Glycemic Control) | Decrease | Limited |
Glimepiride (Medications) | HbA1c (Glycemic Control) | Decrease | Limited |
Glimepiride (Medications) |  Hypoglycemia events (Safety) | Uncertain | Limited |
Metformin (Medications) | Fasting Plasma Glucose (Glycemic Control) | Decrease | Limited |
Metformin (Medications) | HbA1c (Glycemic Control) | Decrease | Limited |
Metformin (Medications) | Hypoglycemia events (Safety) | Uncertain | Limited |
Metformin + glimepiride (Medications) | Daily insulin dose (Glycemic Control) | Increase | Limited |
Metformin + glimepiride (Medications) | Fasting Plasma Glucose (Glycemic Control) | Decrease | Limited |
Metformin + glimepiride (Medications) | HbA1c (Glycemic Control) | Decrease | Strong |
Metformin + glimepiride (Medications) | Hypoglycemia events (Safety) | Uncertain | Limited |
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Evidence Suggest
- HbA1c fell by 1.41% with insulin glargine plus metformin and glimepiride, compared with 0.75% with glargine plus metformin and 0.70% with glargine plus glimepiride.
- Triple therapy lowered HbA1c significantly more than glargine plus metformin and more than glargine plus glimepiride.
- Seventy-five percent of the triple-therapy group reached HbA1c at or below 7.5%, compared with 43.8% in the glargine plus metformin group.
- Rates of symptomatic, nocturnal, and severe hypoglycemia did not differ significantly between treatment groups.
Who this applies to
These findings apply most directly to adults with type 2 diabetes who remain above target despite sulfonylurea plus metformin therapy and are about to start basal insulin. The study population was Korean, non-insulin-treated before enrollment, and relatively lean by usual type 2 diabetes trial standards.
Keep in Mind
This was a short, open-label study, so longer-term durability and safety are still uncertain. The results support the triple combination over 24 weeks, but treatment should still be individualized based on hypoglycemia risk, kidney and liver function, body weight, and how well a patient can manage insulin titration and glucose monitoring.
Between the Lines
- The trial was open-label.
- The sample size was modest at 99 randomized participants.
- Follow-up lasted only 24 weeks.
- The study population was limited to Korean adults with BMI below 30 kg/m2.
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Journal Reference
Park CY, Kang JG, Chon S, Noh J, Oh SJ, Lee CB, Park SW. Comparison between the Therapeutic Effect of Metformin, Glimepiride and Their Combination as an Add-On Treatment to Insulin Glargine in Uncontrolled Patients with Type 2 Diabetes. PLoS One. 2014;9(3):e87799. doi:10.1371/journal.pone.0087799
Sources
Ranked by clinical relevance and evidence quality.
Key References
Most relevant evidence and guidance related to this research.
Management of hyperglycemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)
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