Exenatide improves β-cell function up to 3 years of treatment in patients with type 2 diabetes: a randomised controlled trial

Abstract

Objective: Glucagon-like peptide (GLP)-1 receptor agonist treatment improves β-cell function. In this study, we investigated whether the improvements are sustained during a 3-year treatment period. Research design and methods: Sixty-nine metformin-treated type 2 diabetes patients were randomised to the GLP1 receptor agonist, exenatide (EXE) twice daily (BID) or to insulin glargine (GLAR). β-cell function parameters were derived using the Mari model from standardised breakfast and lunch meals that were administered before treatment, and after 1 and 3 years of treatment. EXE was administered before breakfast. Results: Fifty-nine (EXE: n = 30; GLAR: n = 29) and thirty-six (EXE: n = 16; GLAR: n = 20) patients completed the meal at 1-and 3-year treatment respectively. After 3 years, groups had comparable glycaemic control (HbA1c: EXE 6.6 ± 0.2% and GLAR 6.9 ± 0.2%; P = 0.216). Compared with GLAR, at 1 and 3 years, EXE induced a stronger reduction in post-breakfast glucose concentrations (P < 0.001), with lower C-peptide levels (P < 0.001). Compared with GLAR, EXE increased insulin secretion at 8 mmol/L glucose throughout the study period (P < 0.01). Both treatments improved β-cell glucose sensitivity after 1-year treatment. However, only EXE treatment sustained this improvement for 3 years. No consistent changes in other β-cell parameters including rate sensitivity and potentiation were observed. Conclusions: Compared with GLAR, EXE improved the parameters of β-cell function, especially insulin secretion at 8 mmol/L glucose and β-cell glucose sensitivity, which was sustained during the 3-year treatment period.

The effects of incretin‐based therapies on β‐cell function and insulin resistance in type 2 diabetes: A systematic review and network meta‐analysis combining 360 trials

“…Thus, the importance of preserving β‐cell function and improving insulin resistance in the management of T2DM is highlighted. Our results were consistent with several large clinical trials assessing GLP‐1RAs and DPP‐4Is separately . In one trial specifically designed to determine the effect on β‐cell function, exenatide, a GLP‐1 receptor agonist, was demonstrated to improve β‐cell function, as measured not only by static index (HOMA‐B, fasting C‐peptide), but also by dynamic tests (hyperglycaemic clamps), and the favourable effect was sustained for up to 3 years .…”

Improving glycaemic control in type 2 diabetes: Stimulate insulin secretion or provide beta‐cell rest?

“…[78][79][80] In a head-to-head study with the sulfonylurea glipizide, the SGLT-2 inhibitor dapagliflozin had a lower initial effect on HbA1c reduction (−0.4% vs −0.8%); however, the reduction in glucose levels was more sustained over time with dapagliflozin, resulting in a 0.3% benefit at 208 weeks. 29 Interestingly, the improvement in beta-cell function parameters was sustained during the 3-year treatment period in the 52% of originally randomized patients who completed this small study ( Figure 1D). 84 In addition, reduced appetite limits the size of the ingested meal.…”

“…81 production and glucagon secretion. 29 85 All these factors result in reduced postprandial glucose, and thus insulin levels.…”

“…D, Three-year treatment with the short-acting GLP-1 receptor agonist exenatide, injected before breakfast, provides sustained improvement in beta-cell glucose sensitivity29 In contrast, thiazolidinediones provide durable HbA1c lowering, as illustrated by ADOPT.…”

The albumin-exendin-4 recombinant protein E2HSA improves glycemic control and β-cell function in spontaneous diabetic KKAy mice

“…A large body of clinical research has demonstrated that GLP-1-based drugs provide excellent control of blood glucose levels without dramatic side effects [12–14]. Furthermore, GLP-1 analogs can improve β-cell function, especially in regards to insulin secretion and glucose sensitivity, while promoting β-cell survival by inhibiting apoptosis and enhancing cell proliferation [3, 15, 16]. Six GLP-1 analogs are commercially available as monotherapies for T2DM and are divided into shorting-acting exenatide and lixisenatide, long-acting liraglutide and prolonged-acting exenatide LAR, albiglutide and dulaglutide, based on the duration of action and frequency of injection [3].…”