(DCP059) SAFETY AND EFFICACY OF TIRZEPATIDE FOR SURPASS-2 THROUGH -5 PARTICIPANTS OVER 65 YEARS OLD WITH BMI BELOW 30 KG/M2: A POST-HOC ANALYSIS

Background: Tirzepatide (TZP) is a once-weekly glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonist approved as a treatment for adults with type 2 diabetes (T2D) and under investigation for chronic weight management. The Phase 3 SURPASS 1-5 studies showed safety and efficacy of TZP in improvement of glycaemic control and body weight (BW) reduction in adults with T2D. The effects of TZP in older participants without obesity are unknown. This post hoc analysis investigated the glycaemic-lowering and BW-reduction effects of TZP in adults ≥65 yrs old with BMI < 30 kg/m2 in SURPASS 2-5.

METHODS AND RESULTS: Primary and key secondary endpoints were assessed at week 40 (SURPASS-2, -5) or week 52 (SURPASS-3, -4) in participants randomized to TZP 5, 10, or 15mg. Subgroup analysis (patients ≥65 yrs old with BMI < 30 kg/m2) was done on the modified intent-to-treat population (all randomised patients who received ≥1 dose of study drug) and included data while on treatment with data after rescue medication censored (efficacy estimand). HbA1c and BW changes at endpoint with TZP 5, 10, and 15 mg in this subgroup were evaluated descriptively. Adverse events (AE) were also assessed.
Baseline (BL) demographics of this subgroup population included a range of mean age 68.8-71.6 yrs, weight 71.0-76.6 kg, BMI 26.7-27.9 kg/m2, 35.0-72.2% were male, and 52.6-90.3% were White. Mean HbA1c reduction from BL for all TZP doses ranged from 1.7-2.3% from mean BLs of 7.91%-8.58%, similar to that for the full study population (1.9-2.6%). Mean subgroup BW reductions from BL for all TZP doses ranged from 5.1-8.6 kg (6.9-11.5%). Previously reported BW reductions for the full population ranged from 6.2-12.9 kg (6.6-13.9%). The most frequent AEs for the subgroup were gastrointestinal-related (GI), similar to that reported for the full study population. In participants treated with TZP in the subgroup, hypoglycaemic events with blood glucose < 3.0 mmol/L or severe hypoglycaemia were highest when used with insulin or sulphonylurea and ranged from 0-0.70/yr, similar to that reported for the full study population.

Conclusion: Participants ≥65 yrs old with BMI < 30 kg/m2 treated with TZP experienced glycaemic and BW reductions. The most frequent AEs were GI in nature, consistent with that of the overall study population. Risk of hypoglycaemia was not worsened in this subgroup. Treatment with TZP resulted in glycaemic and weight improvements and without substantial differences in tolerability in a population that may require special considerations due to increased comorbidities and disease burden.