Open-label or unblinded (moderate): Open-label design

Industry funded (moderate): Industry funding reported

HbA1c fell from 8.5% to 7.7% over 24 weeks with insulin glargine plus metformin. This was a meaningful within-group improvement, but it was smaller than the reduction seen with the triple-combination arm.

Fasting plasma glucose decreased from 9.0 to 6.9 mmol/L in the metformin arm. Fasting glucose improved clearly, although between-group differences were not statistically significant.

Any hypoglycemia occurred in 45.5% of patients in this arm, and the frequency did not differ significantly from the other treatment groups. The trial did not show a clear safety advantage or disadvantage for hypoglycemia here.

Fixed-dose metformin XR 1500 mg/day continued as add-on therapy to morning insulin glargine.

HbA1c fell from 8.4% to 7.7% in the glimepiride arm over 24 weeks. This improved glycemic control, but it was not as strong as the reduction achieved with the metformin-plus-glimepiride arm.

Fasting plasma glucose decreased from 8.9 to 7.6 mmol/L in the glimepiride arm. The decline was favorable within the group, although it was not clearly better than the other regimens.

Any hypoglycemia occurred in 58.8% of patients in this arm, but the overall difference across study groups was not statistically significant. The study therefore did not show a clear difference in hypoglycemia burden for this regimen.

Fixed-dose glimepiride 4 mg/day continued as add-on therapy to morning insulin glargine.

HbA1c fell from 8.7% to 7.3% with insulin glargine plus metformin and glimepiride. This reduction was significantly larger than the change seen with either glargine plus metformin alone or glargine plus glimepiride alone.

Fasting plasma glucose decreased from 9.2 to 6.8 mmol/L in the triple-therapy arm. The improvement was clinically favorable, but the between-group comparison for fasting glucose was not statistically significant.

Any hypoglycemia occurred in 53.1% of patients in the triple-therapy arm, with no significant difference from the other groups. Severe hypoglycemia was not reported in any arm.

Insulin dose increased from 12.5 to 20.1 units in the triple-therapy arm, but this final requirement was lower than in the two dual-therapy groups. That pattern suggests glycemic benefit with less insulin escalation.

Fixed-dose metformin XR 1500 mg/day plus glimepiride 4 mg/day continued together as add-on therapy to morning insulin glargine.

Positive: 7; Negative: 0; No effect: 3; Mixed: 0

Extracted 10 outcome signals across the study

All three regimens improved glycemia, but the metformin plus glimepiride combination with insulin glargine delivered the strongest HbA1c benefit while hypoglycemia and weight gain remained broadly similar.

HbA1c ↓ most with insulin glargine plus metformin and glimepiride

Fasting plasma glucose ↓ in all three treatment groups

Mostly intermediate or surrogate outcomes

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.

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

The sample size was modest at 99 randomized participants.

The study population was limited to Korean adults with BMI below 30 kg/m2.

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.

HbA1c ≤7.5% ↑ more often with triple therapy

Hypoglycemia ↔ stayed broadly similar across groups

This consensus report outlines when to intensify therapy in type 2 diabetes and emphasizes individualizing treatment choices, including when basal insulin and combination drug strategies should be considered.

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)

This randomized trial provides a direct comparison point for insulin glargine added to metformin and sulfonylurea therapy in type 2 diabetes, helping place the current glargine-based combination results into a broader treatment context.

Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (LEAD-5 met+SU)

This add-on therapy study in type 2 diabetes offers another active-comparator benchmark for how much extra glycemic improvement can be expected when basal or background therapy is intensified with an additional glucose-lowering agent.

Diabetes Care - Matthaei et al. 2015 - Dapagliflozin Add-on Study

High dropout rate (moderate): 20.2% dropout

Includes self-reported outcomes (moderate): Self-reported outcomes used

No post-intervention follow-up (moderate): 0 weeks of follow-up after treatment ended

Metformin and glimepiride with basal insulin lowered HbA1c the most

This trial compared three ways to add oral diabetes drugs to insulin glargine. Keeping both metformin and glimepiride alongside glargine lowered HbA1c the most, while fasting glucose improved in all groups and hypoglycemia rates stayed broadly similar.

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.

Which oral add-on regimen works best with insulin glargine in uncontrolled type 2 diabetes

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.

Metformin and glimepiride with basal insulin lowered HbA1c the most

Public Library of Science

Summary

Study Design

Interventions

Study Type

Outcomes

Duration and Size

Study Population

Age Range

Sex

Geography

Other Criteria

Comparison with other Studies

Journal Reference

Stay informed. Stay ahead.