Liraglutide treatment in overweight and obese patients with type 1 diabetes: A 26‐week randomized controlled trial; mechanisms of weight loss

Abstract

Aim To investigate the effects of liraglutide treatment on glycaemic control and adipose tissue metabolism in overweight and obese people with type 1 diabetes (T1DM). Research design and methods A total of 84 adult overweight and obese patients with T1DM, with no detectable C‐peptide, were randomized (1:1) to either placebo or 1.8 mg/d liraglutide for 6 months. Blood samples were collected at 0, 12 and 26 weeks. Subcutaneous adipose tissue biopsies, a high‐calorie high‐fat meal challenge test, continuous glucose monitoring, dual‐energy X‐ray absorptiometry and MRI were performed before and at the end of treatment. Results In all, 37 and 27 patients who received liraglutide and placebo, respectively, completed the study. Glycated haemoglobin fell by 0.41 ± 0.18% (4.5±1.4 mmol/mol) from baseline after liraglutide treatment (P = 0.001), and by 0.29 ± 0.19% (3.1±2.0 mmol/mol) compared to placebo (P = 0.1). There was no increase in hypoglycaemia, while the time spent in normal glycaemia increased (P = 0.015) and time spent in hyperglycaemia decreased (P = 0.019). Body weight fell significantly in the liraglutide group, mostly in the form of fat mass loss (including visceral fat), with no change in lean mass. Systolic blood pressure (SBP) also fell after liraglutide treatment. Liraglutide also caused a significant increase in the expression of adipose tissue triglyceride lipase, carnitine palmitoyl transferase‐1, peroxisome proliferator‐activated receptor (PPAR)α, PPARδ, uncoupling protein‐2 and type 2 iodothyronine deiodinase in the adipose tissue. Conclusions Liraglutide improves glycaemia, reduces adiposity and SBP. Liraglutide also stimulates mechanisms involved with an increase in lipid oxidation and thermogenesis, while conserving lean body mass.

The impact of pharmacological and lifestyle interventions on body weight in people with type 1 diabetes: A systematic review and meta‐analysis

“…For these studies, the mean age of participants was 43.9 (SD 13.6) years, with a duration of diabetes of 21.5 (SD 12.5) years, body weight 83.2 (SD 16.7) kg and an HbA1c of 8.1% (SD 0.8%) (65.5 mmol/mol). Changes in body composition‐related measurements were reported in four studies 38–41 (S12 and S13). The ethnicity of participants was documented in most studies and mainly as Caucasian, with a few studies including black African Americans and Asians (Table S8).…”

“…Out of 33 studies, 11 reported arterial blood pressure at baseline and postintervention 13,37,40,41,49,50,56,57,66–68 (Tables S23 and S24). Four of the 11 studies reported a significant decrease in either systolic or diastolic blood pressure or both from baseline for within groups and difference versus placebo 40,41,49,56 …”

“…The ethnicity of participants was documented in most studies and mainly as Caucasian, with a few studies including black African Americans and Asians (Table S8). Studies were mostly parallel group RCTs, 37,38,42–58 with some crossover trials 40,59–61 and other randomized trials 39,41,62 . The intervention group received the drug (liraglutide, exenatide, sotagliflozin, canagliflozin, ipragliflozin, empagliflozin, dapagliflozin, sitagliptin or metformin) in different oral doses or by injection as appropriate (Table S10).…”

“…The GLP‐1 receptor agonist studies used liraglutide in three different strengths/doses (0.6, 1.2 and 1.8 mg), with the study duration ranging from 12 to 52 weeks (Table S6). For the seven studies assessing liraglutide, the inclusion criteria for BMI were 18‐28, 37 ≥25, 40,41,50 ≤27 or greater than 27 kg/m 2 , 46 but were not reported in two studies 48,49 . For the three studies assessing exenatide, the inclusion criteria for BMI were 20‐30 60,61 or 18‐27 kg/m 2 39 …”

“…Out of 33 studies, all except one 65 reported total insulin daily doses at baseline and intervention (Tables S21 and S22). Twenty‐one studies reported a significant decrease in TIDD levels from baseline compared with that within groups or the difference versus placebo 13,39,41–43,45,46,48–53,55,56,58–61,64,68 …”