GLP-1 receptor agonist is effective and safe in elderly type 2 diabetic patients
Semaglutide had a comparable efficacy and safety profile in non-elderly and elderly patients with type 2 diabetes.
Semaglutide as a therapeutic option for elderly patients with type 2 diabetes: pooled analysis of the SUSTAIN 1–5 trialsLiterature - Warren M, Chaykin L, Trachtenbarg D, et al. - Diabetes Obes Metab 2018; published online ahead of print
Introduction and methods
Elderly patients with type 2 diabetes (T2DM) are at increased risk of hypoglycemia [1]. Semaglutide, a human GLP-1 analogue, reduces HbA1c and body weight (BW), either as monotherapy once weekly, or combined with other antidiabetic treatments, and is well tolerated in general [2-6].
In this pooled analysis of the SUSTAIN studies, the efficacy and safety of semaglutide was evaluated in elderly (≥65 years) vs non-elderly (<65 years) T2DM patients. In SUSTAIN 1-5, 3045 patients with T2DM were randomized to once-weekly subcutaneous semaglutide (0.5 mg or 1.0 mg) or comparators (placebo, sitagliptin, exenatide or insulin).
Main results
- With semaglutide 0.5 mg, HbA1c reductions ranged from 1.2 to 1.5% (non-elderly) and 1.3 to 1.5% (elderly) and from 1.5 to 1.9% (non-elderly) and 1.2 to 1.8% (elderly) with semaglutide 1.0 mg. For comparators, the range of reduction was 0.0 to 0.9% (non-elderly) and 0.2 to 1.0% (elderly).
- In non-elderly, the estimated treatment difference (ETD) vs comparator ranged from –0.37 to –1.50% for semaglutide 0.5 mg and –0.62 to –1.87% for semaglutide 1.0 mg. In elderly, ETDs ranged from –0.43 to –1.35% and –0.50 to –1.55%, respectively.
- In non-elderly, HbA1c <7.0% was achieved by a larger proportion of patients treated with semaglutide 0.5 mg (54–70%) and 1.0 mg (65–78%) vs comparators (11–36%). In the elderly group, the corresponding proportions were 69–92%, 67–86% vs 11–51%, respectively.
- With semaglutide 0.5 mg, BW reductions ranged from 3.3 to 4.3 kg (non-elderly) and 3.6 to 4.6 kg (elderly), and from 4.6 to 6.4 kg (non-elderly) and 4.1 to 6.7 kg (elderly) with semaglutide 1.0 mg. With comparators, BW ranged from +1.1 to –2.1 kg (non-elderly) and +1.5 to –1.7 kg (elderly).
- The proportion of patients experiencing AEs was comparable between the age groups. The proportion of patients prematurely discontinuing treatment due to AEs was higher in the elderly than the non-elderly group, and in the semaglutide vs comparator arms for both groups.
- The rate (events per 100 exposure years) of severe hypoglycemia events was similar between age groups in the semaglutide arms, except for in SUSTAIN-5 where patients were on a background of basal insulin therapy.
Conclusion
Semaglutide consistently improved HbA1c and BW vs comparators, in elderly (≥65 years) and non-elderly patients with T2DM, and was well tolerated, suggesting that semaglutide may be an effective treatment option for elderly T2DM patients.
References
1. Du YF, Ou HY, Beverly EA, et al. Achieving glycemic control in elderly patients with type 2 diabetes: a critical comparison of current options. Clin Interv Aging. 2014;9:1963-1980.
2. Ahren B, Masmiquel L, Kumar H, et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. The lancet
Diabetes & endocrinology. 2017;5(5):341-354.
3. Ahmann AJ, Capehorn M, Charpentier G, et al. Efficacy and safety of once-weekly semaglutide vs. exenatide ER in patients with type 2 diabetes (SUSTAIN 3). American Diabetes Association 76th Scientific Sessions; 2016; New Orleans, Louisiana, USA.
4. Aroda VR, Bain SC, Cariou B, et al. Efficacy and safety of once-weekly semaglutide versus once daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naïve patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol. 2017;5(5):355-366.
5. Rodbard H LI, Reed J, de la Rosa R, et al. Efficacy and safety of semaglutide once-weekly vs placebo as add-on to basal insulin alone or in combination with metformin in patients with type 2 diabetes (SUSTAIN 5). Diabetologia. 2016;Suppl 1(59):S364-365.
6. Sorli C, Harashima SI, Tsoukas GM, et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial. The lancet Diabetes & endocrinology. 2017;5(4):251-260.