Comparison of the Continuous Glucose Monitoring Profiles of Four Glucose-Lowering Medications in the GRADE Randomized Trial

Incretin-based drugs liraglutide and sitagliptin produced the most favorable continuous glucose monitoring profiles when added to metformin in adults with type 2 diabetes: they had the highest time in range, the least hypoglycemia, and the best achievement of CGM-based targets. Insulin glargine and glimepiride caused more glucose variability and hypoglycemia even at the same HbA1c. These findings come from a CGM substudy of 1,080 participants in the randomized GRADE trial.

Randomized controlled trial — Randomized controlled trial, comparative study, CGM substudy. Population: Adults with type 2 diabetes taking metformin in the GRADE study. Sample size: 1,080 participants. Follow-up: 5 ± 1.3 years of follow-up; 2-week masked CGM substudy midstudy. Interventions: insulin glargine (added to metformin); glimepiride (added to metformin); liraglutide (added to metformin); sitagliptin (added to metformin). Cited by 1 other paper.

Among 1,080 participants, the sitagliptin and liraglutide groups had the highest TIR70-180 and lowest time below range, with more participants achieving TIR >70% and TBR<70 <4% (P < 0.001). Insulin glargine and glimepiride had higher %CV and TBR<70 within each HbA1c stratum, while mean glucose did not differ among treatments by HbA1c. The authors concluded that incretin-class drugs had the lowest %CV, the least hypoglycemia, and the best achievement of CGM targets.

Researchers focused on liraglutide will care because this randomized head-to-head comparison places liraglutide among the incretin drugs with the most favorable CGM profile: lowest glucose variability, least hypoglycemia, and best achievement of CGM targets compared with glimepiride or insulin glargine, despite similar mean glucose at each HbA1c level. The paper does not establish liraglutide's effects on HbA1c, safety, or long-term clinical outcomes beyond the midstudy CGM snapshot, and it reports no dosing or adherence information.

Key findings

• Sitagliptin and liraglutide had the highest TIR70-180 and the lowest time below range among the four add-on medications.
• Liraglutide and sitagliptin had higher proportions of participants achieving CGM targets of TIR >70% and TBR<70 <4% (P < 0.001).
• Within each HbA1c stratum, insulin glargine and glimepiride had higher %CV and TBR<70 than liraglutide and sitagliptin.
• Mean glucose did not differ among the four treatments when stratified by HbA1c.
• The incretin-class drugs had the lowest %CV, the least hypoglycemia, and the best achievement of CGM targets.

Limitations

• No limitations were stated in the abstract.
• The CGM substudy was a 2-week masked measurement at one midstudy time point, not full follow-up.
• CGM data were reported for only 1,080 of the GRADE participants, so the substudy may not represent the full cohort.
• All arms also received metformin, so effects are limited to add-on combinations, not monotherapy.

The record

• Journal: Diabetes care 49(6): 981-989
• Published: 2026-05-25
• PMID: 41925680 — DOI: 10.2337/dc25-3055
• MeSH terms: Humans, Diabetes Mellitus, Type 2, Metformin, Sulfonylurea Compounds, Blood Glucose, Hypoglycemic Agents, Middle Aged, Female, Male, Sitagliptin Phosphate, Liraglutide, Insulin Glargine, Glycated Hemoglobin, Continuous Glucose Monitoring
• Funding: NIDDK NIH HHS; American Diabetes Association; NHLBI NIH HHS; CDC HHS; National Heart, Lung, and Blood Institute; Division of Diabetes, Endocrinology, and Metabolic Diseases; Division of Diabetes, Endocrinology, and Metabolic Diseases; Centers for Disease Control and Prevention

Peptide profiles: Liraglutide.

All indexed evidence: Liraglutide trials & papers.

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