Metformin and glimepiride with basal insulin lowered HbA1c the most

Moderate confidence

some concerns bias

Last updated May 6, 2026

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