Combination therapy with GLP-1 analogues and SGLT-2 inhibitors in the management of diabesity: the real world experience

Abstract

Diabesity-obesity resulting in diabetes-is a major health problem globally because of the obesity epidemic. Several anti-diabetic medications cause weight gain and may worsen obesity, and possibly diabeisty. Two recent small retrospective cohort studies showed weight loss and diabetes improvement with combination of glucagon-like peptide-1 (GLP-1) agonists and sodium-glucose co-transporter type-2 (SGLT-2) inhibitors in obese subjects. We assessed the effect of combination therapy with GLP-1 agonists and SGLT-2 inhibitors in the management of diabesity in a retrospective study at the Wolverhampton Diabetes Centre. Out of 79 patients on this combination regimen with other anti-diabetic medications, 37 cases who had follow up at 3-6 months were studied. Mean age and duration of follow up were 57.4 (+/-7.8) and 139 (+/-32.6) days, respectively. Twenty-two patients (59.5 %) were Asians. Statistically significant improvements in clinical parameters such as body weight reduction (3.07 kg), glycated haemoglobin (HbA1c) reduction (1.05 %), lower BMI (-1.13 kg/M) and insulin dose reduction (6.8 units) were observed (p < 0.05 for all) in patients on combination regimen. Linear regression analysis showed that baseline HbA1c and baseline insulin dose were independent predictors of HbA1c reduction and insulin dose reduction, respectively. Our results suggest that combination therapy with GLP-1 agonists and SGLT-2 inhibitors is a promising option for patients with diabesity.

Safety and Efficacy of Exenatide Once Weekly Plus Dapagliflozin Once Daily Versus Exenatide or Dapagliflozin Alone in Patients With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy: 52-Week Results of the DURATION-8 Randomized Controlled Trial

“…A randomized, placebo-controlled study combining exenatide QW and dapagliflozin in participants who were obese without diabetes reported significant weight loss, BP reduction, and glucose normalization without unexpected AEs (22). Findings from real-world observational and retrospective analyses further support the use of these two drug classes in combination (23)(24)(25)(26)(27)(28). Although having a different design to DURATION-8, the recent Assessment of Weekly Administration of LY2189265 (dulaglutide) in Diabetes-10 (AWARD-10) trial among patients with inadequately controlled type 2 diabetes receiving an SGLT2 inhibitor with or without metformin demonstrated improved glycemic control with add-on dulaglutide therapy versus placebo (29).…”

Long‐term safety and efficacy of the sodium–glucose cotransporter 2 inhibitor, tofogliflozin, added on glucagon‐like peptide‐1 receptor agonist in Japanese patients with type 2 diabetes mellitus: A 52‐week open‐label, multicenter, post‐marketing clinical study

“…Recent small retrospective cohort studies showed clinical benefits, including weight loss and diabetes improvement, with the combination of GLP‐1 receptor agonists and SGLT2 inhibitors. The combination of dapagliflozin with GLP‐1 receptor agonist was reported to be generally well tolerated, and significantly reduced the mean HbA1c levels and bodyweight in patients with type 2 diabetes mellitus, with a significant decrease in blood pressure, a significant increase of TC and HDL‐C, and a decrease of TG Deo et al reported a retrospective study of combination therapy of GLP‐1 receptor agonists with SGLT2 inhibitors for the management of diabesity, resulting in significant improvements in clinical parameters, such as bodyweight loss (3.1 kg), HbA1c reduction (1.1%), lower BMI (−1.1 kg/m 2 ) and insulin dose reduction (6.8 units), but the combination therapy was not associated with a reduction in blood pressure. Co‐administration of a GLP‐1 receptor agonist (exenatide) and a SGLT2 inhibitor (dapagliflozin) improved various glycemic variables and cardiovascular risk factors in patients with type 2 diabetes mellitus inadequately controlled by metformin monotherapy.…”

Beneficials Effects of Canagliflozin in a Weight-Centered Management in Patients with Type 2 Diabetes Mellitus in Real Practice

“…This study reports a significant decrease in mean HbA1c of 1.3% at 12 months with the addition of canagliflozin to anti-diabetic therapy, superior to Phase III trials (where canagliflozin 100 mg and 300 mg reduced HbA1c from -0.58% to -1.03%) [12] and others real-world studies [12][13][14][15][16][17]. Probably weight loss over a short-term period (12 months) is associated with a positive impact on attainment of HbA1c goals [19,20], but our patients with weight loss ≥ 5% or ≥ 10% at 12 months did not result in additional reductions in HbA1c levels (Table 3).…”

“…Multiple studies have demonstrated that treatment with canagliflozin result in significant reductions of HbA1c from baseline by -0.58% and -1.03% and in body weight by -3.3% and -4.4% after 52 weeks with 100 and 300 mg, respectively, in patients with diabetes [12]. However, at present there is little information in real world relating about benefits and safety of canagliflozin in a weight-centered management in specialty diabetes practice settings [13][14][15][16][17]. The aim of this study was to evaluate the real-world efficacy and safety of canagliflozin in patients with T2DM, associated to a weight-loss intensive lifestyle intervention program, to achieve weight loss greater than 5% at 12 months.…”