The effects of glucagon‐like peptide (GLP)‐1 receptor agonists on weight and glycaemic control in Prader–Willi syndrome: A systematic review

Abstract

Objective The mainstay management of hyperphagia and obesity in Prader–Willi syndrome (PWS) relies on dietary restrictions, strict supervision and behavioural modifications, which can be stressful for the patient and caregiver. There is no established pharmacological strategy to manage this aspect of PWS. Theoretically, glucagon‐like peptide‐1 (GLP‐1) receptor agonists (GLP1‐RA) used in patients with obesity and type 2 diabetes mellitus (T2DM) may be efficacious in weight and glycaemic control of PWS patients. We conducted a systematic review of the literature to summarize the evidence on the use of GLP1‐RA in PWS patients. Design Primary studies were searched in major databases using key concepts ‘Prader–Willi syndrome’ and ‘GLP1 receptor agonist’ and outcomes, ‘weight control OR glycaemic control OR appetite regulation’. Results Ten studies included, summarizing GLP1‐RA use in 23 PWS patients (age, 13–37 years), who had used either exenatide (n = 14) or liraglutide (n = 9) over a duration of 14 weeks to 4 years. Sixteen (70%) of these patients had T2DM. Ten patients experienced improvement in body mass index, ranging from 1.5 to 16.0 kg/m2, while improvement in HbA1c was seen in 19 of 23 cases, ranging between 0.3% and 7.5%. All five studies reporting appetite or satiety showed improvement in satiety levels. There were no reported serious side effects. Conclusions GLP1‐RA appears safe in PWS patients and may have potential benefits for weight, glycaemic and appetite control. Nonetheless, we also highlight a significant gap in the literature on the lack of well‐designed studies in this area, which limits the recommendation of GLP1‐RA use in PWS patients at present.

Endocrine and Metabolic Illnesses in Young Adults with Prader–Willi Syndrome

“…Furthermore, 10 patients were treated with a combination therapy of a glucagon-like peptide 1 (GLP-1) receptor agonist due to uncontrolled diabetes. A recent systematic review has shown that GLP-1 receptor agonists are safe in patients with PWS and may potentially help with weight reduction, blood sugar control, and appetite control [ 15 ]. In our cohort, GLP-1 receptor agonists appeared to be well tolerated with no serious adverse effects; however, four patients discontinued the injections because their parents did not feel they had a significant effect on appetite, although these patients had a slightly lowered Hba1c during the early phase of the injection.…”

Evaluating the Efficacy of Pharmacological Therapy for Prader-Willi Syndrome: A Systematic Review and Meta-analysis

“…51,52) which accounts for 7% of the causes of death in patients with PWS. 47) Previous metaanalysis or systematic review results for BMI were various, [12][13][14][15] our study showed a nonsignificant decrease in BMI. These results may be caused by nonsignificant increments in weight and obvious increments in height.…”

“…8) In previous systematic reviews and meta-analysis, the effects of pharmacological treatments on body composition variables such as height, BMI, and FM have evaluated. [12][13][14][15] As a result of previous meta-analysis, increased LBM and decreased FM were consistently observed. [12][13][14][15] Since previous studies have investigated randomized controlled trials (RCTs) and nonrandomized controlled trials (NRCTs) simultaneously, [12][13][14][15] biases were unpreventable.…”

“…[12][13][14][15] As a result of previous meta-analysis, increased LBM and decreased FM were consistently observed. [12][13][14][15] Since previous studies have investigated randomized controlled trials (RCTs) and nonrandomized controlled trials (NRCTs) simultaneously, [12][13][14][15] biases were unpreventable. Moreover, there are additional studies that have been investigated the efficacy of pharmacological treatment in PWS patients but are not included in the previous meta-analysis.…”

Intensive management of obesity in people with Prader-Willi syndrome

“…Limited data exist on the outcomes of intensive weight loss interventions in individuals with PWS. Case reports and case series have documented successful weight loss following initiation of GLP-1 receptor agonists [ 7 , 8 ], but data regarding other options are limited. As such, the aims of this retrospective review of real-world clinical data are to examine the efficacy, safety, and tolerability of intensive medical weight loss interventions in individuals with PWS.…”