Age and Sex Differences in Efficacy of Treatments for Type 2 Diabetes: A Network Meta-Analysis
Authors' conclusion
The SGLT2 inhibitors and GLP-1 receptor agonists were associated with lower risk of MACEs. Analysis of age × treatment interactions suggested that SGLT2 inhibitors were more cardioprotective in older than in younger people despite smaller reductions in HbA1c; GLP-1 receptor agonists were more cardioprotective in younger people.
Study context
- Population
- Adults with T2D in RCTs; Hemoglobin A1c (HbA1c) trials mean age 58.9 years, 42.3% female; MACE trials mean age 64.0 years, 35.3% female601 eligible trials
- Comparison
- SGLT2i, GLP-1 RA or DPP-4i vs placebo or active comparator, by age and sex
- Outcome
- HbA1c and major adverse cardiovascular events (MACEs) (age × treatment and sex × treatment interactions)
Methodological detailsindividual participant and aggregate data, multilevel network meta-regression, age × treatment and sex × treatment interactions, IPD obtained for 103 trials (103 reported HbA1c, 6 reported MACE), 592 trials with 309 503 participants reported HbA1c; 23 trials with 168 489 participants reported MACE
- Individual participant and aggregate data
- Multilevel network meta-regression
- Age × treatment and sex × treatment interactions
- IPD obtained for 103 trials (103 reported HbA1c, 6 reported MACE)
- 592 trials with 309 503 participants reported HbA1c; 23 trials with 168 489 participants reported MACE
Pooled result
As reported in the abstract
Age × treatment interaction, per 30-year increment in age
- SGLT2i vs placebo: less HbA1c lowering with increasing age, monotherapy
- AR 0.24% (0.10% to 0.38%) (95% CrI)
- SGLT2i: less HbA1c lowering with age, dual therapy
- AR 0.17% (0.10% to 0.24%) (95% CrI)
- SGLT2i: less HbA1c lowering with age, triple therapy
- AR 0.25% (0.20% to 0.30%) (95% CrI)
- GLP-1 RA: greater HbA1c lowering with age, monotherapy
- AR −0.18% (−0.31% to −0.05%) (95% CrI)
- GLP-1 RA: greater HbA1c lowering with age, dual therapy
- AR −0.24% (−0.40% to −0.07%) (95% CrI)
- GLP-1 RA: not for triple therapy
- AR 0.04% (−0.02% to 0.11%) (95% CrI)
- DPP-4i: slightly better HbA1c lowering in older people, dual therapy
- AR −0.09% (−0.15% to −0.03%) (95% CrI)
- DPP-4i: not for monotherapy
- AR −0.08% (−0.18% to 0.01%) (95% CrI)
- DPP-4i: not for triple therapy
- AR −0.01% (−0.06% to 0.05%) (95% CrI)
- SGLT2i: relative MACE reduction greater in older vs younger, per 30-year increment
- HR 0.76 (0.62 to 0.93) (95% CrI)
- GLP-1 RA: relative MACE reduction less in older vs younger
- HR 1.47 (1.07 to 2.02) (95% CrI)
Original publication
Age and Sex Differences in Efficacy of Treatments for Type 2 Diabetes: A Network Meta-Analysis. JAMA. Published 25 March 2025. doi:10.
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