Glucagon-like Peptide-1 Receptor Agonist Therapy Research Articles

Markers of β-Cell Failure Predict Poor Glycemic Response to GLP-1 Receptor Agonist Therapy in Type 2 Diabetes.

To assess whether clinical characteristics and simple biomarkers of β-cell failure are associated with individual variation in glycemic response to GLP-1 receptor agonist (GLP-1RA) therapy in patients with type 2 diabetes. We prospectively studied 620 participants with type 2 diabetes and HbA1c ≥58 mmol/mol (7.5%) commencing GLP-1RA therapy as part of their usual diabetes care and assessed response to therapy over 6 months. We assessed the association between baseline clinical measurements associated with β-cell failure and glycemic response (primary outcome HbA1c change 0-6 months) with change in weight (0-6 months) as a secondary outcome using linear regression and ANOVA with adjustment for baseline HbA1c and cotreatment change. Reduced glycemic response to GLP-1RAs was associated with longer duration of diabetes, insulin cotreatment, lower fasting C-peptide, lower postmeal urine C-peptide-to-creatinine ratio, and positive GAD or IA2 islet autoantibodies (P ≤ 0.01 for all). Participants with positive autoantibodies or severe insulin deficiency (fasting C-peptide ≤0.25 nmol/L) had markedly reduced glycemic response to GLP-1RA therapy (autoantibodies, mean HbA1c change -5.2 vs. -15.2 mmol/mol [-0.5 vs. -1.4%], P = 0.005; C-peptide <0.25 nmol/L, mean change -2.1 vs. -15.3 mmol/mol [-0.2 vs. -1.4%], P = 0.002). These markers were predominantly present in insulin-treated participants and were not associated with weight change. Clinical markers of low β-cell function are associated with reduced glycemic response to GLP-1RA therapy. C-peptide and islet autoantibodies represent potential biomarkers for the stratification of GLP-1RA therapy in insulin-treated diabetes.

The Effect of Glucagon-Like Peptide 1 Receptor Agonists on Weight Loss in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison Meta-Analysis.

AimsTo determine the effects of glucagon-like peptide-1 receptor agonists compared with placebo and other anti-diabetic agents on weight loss in overweight or obese patients with type 2 diabetes mellitus.MethodsElectronic searches were conducted for randomised controlled trials that compared a glucagon-like peptide-1 receptor agonist therapy at a clinically relevant dose with a comparator treatment (other type 2 diabetes treatment or placebo) in adults with type 2 diabetes and a mean body mass index ≥ 25kg/m2. Pair-wise meta-analyses and mixed treatment comparisons were conducted to examine the difference in weight change at six months between the glucagon-like peptide-1 receptor agonists and each comparator.ResultsIn the mixed treatment comparison (27 trials), the glucagon-like peptide-1 receptor agonists were the most successful in terms of weight loss; exenatide 2mg/week: -1.62kg (95% CrI: -2.95kg, -0.30kg), exenatide 20μg: -1.37kg (95% CI: -222kg, -0.52kg), liraglutide 1.2mg: -1.01kg (95%CrI: -2.41kg, 0.38kg) and liraglutide 1.8mg: -1.51 kg (95% CI: -2.67kg, -0.37kg) compared with placebo. There were no differences between the GLP-1 receptor agonists in terms of weight loss.ConclusionsThis review provides evidence that glucagon-like peptide-1 receptor agonist therapies are associated with weight loss in overweight or obese patients with type 2 diabetes with no difference in weight loss seen between the different types of GLP-1 receptor agonists assessed.

Effects of the GLP-1 Receptor Agonist Dulaglutide on the Structure of the Exocrine Pancreas of Cynomolgus Monkeys.

Clinical and nonclinical studies have implicated glucagon-like peptide-1 (GLP-1) receptor agonist therapy as a risk factor for acute pancreatitis in patients with type 2 diabetes. Therefore, it is critical to understand the effect that dulaglutide, an approved GLP-1 receptor agonist, has on the exocrine pancreas. Dulaglutide 8.15 mg/kg (approximately 500 times the maximum recommended human dose based on plasma exposure) was administered twice weekly for 12 months to cynomolgus monkeys. Serum amylase and lipase activities were measured and 6 sections of each pancreas were examined microscopically. Ductal epithelial cell proliferation was estimated using Ki67 labeling. Dulaglutide administration did not alter serum amylase or lipase activities measured at the end of treatment compared to control values. An extensive histologic evaluation of the pancreas revealed no changes in the acinar or endocrine portions and no evidence of pancreatitis, necrosis, or pancreatic intraepithelial neoplasia. An increase in goblet cells noted in 4 of the 19 treated monkeys was considered an effect of dulaglutide but was not associated with dilation, blockage, or accumulation of mucin in the pancreatic duct. There was no difference in cell proliferation in ductal epithelium between control and dulaglutide-treated monkeys. These data reveal that chronic dosing of nondiabetic primates with dulaglutide does not induce inflammatory or preneoplastic changes in exocrine pancreas.

OC-072 Does endoscopic duodenal-jejunal exclusion improve non-alcoholic fatty liver disease (nafld) in patients with diabesity?

Introduction The rapidly increasing global prevalence of NAFLD paralleling the diabesity pandemic demands that new effective therapies are identified. The aim of this study was to investigate the impact of an endoscopic duodenal-jejunal liner (DJL) (endobarrier) with or without glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy on NAFLD. Method Adults with type 2 diabetes and obesity despite GLP-1RA therapy (HbA1c ≥7.5%, BMI ≥35 kg/m 2 ) were randomised to (1) DJL+GLP1RA (liraglutide 1.2 mg daily) therapy; (2) DJL alone; (3) escalated dose liraglutide (1.8 mg daily). Descriptive statistics were performed (%frequency, mean ±SD, median (IQR)). Changes in weight, HbA1c (paired t-test) and non-invasive composite scores (NAFLD fibrosis score (NFS) and AST to platelet ratio index (APRI) score) were calculated over 3 months within groups (Wilcoxon test). A sub-group underwent magnetic resonance imaging (MRI) to evaluate hepatic fat fraction over 4 months of DJL implant (paired t-test). Hepatic fat fraction (HFF) was calculated by comparing the in-phase/ out-of-phase signal by 3 blinded independent assessors using 3 regions of interest in the liver. Results Of 40 patients (age 51.2 ± 10.0 years, 40.0% male, 60.0% Caucasian, baseline BMI 41.4 ± 4.9 kg/m 2 , HbA1c 78 ± 16 mmol/mol (9.3 ± 1.4%)), baseline ALT was 27 (17.8–41.0) IU/l, AST 21 (17.8–41.5) IU/l, ƔGT 35 (22.0–71.5) IU/l and 82.5% had a NFS regarded as at intermediate (65.0%) or high risk (17.5%) for fibrosis. Over 3 months, there was a reduction in weight by 7.3 ± 4.0 kg and in HbA1c by 14.5 ± 15.3 mmol/mol (1.3 ± 1.4%), P Conclusion There was a high prevalence of NAFLD in this group of patients with diabesity. Despite previous suboptimal response to GLP1RA therapy there was improvement in NFS and APRI scores in those treated with DJL+GLP1RA and DJL alone, the latter group demonstrating a superior response. Implantation of DJL was effective at reducing HFF. These data suggest duodenal exclusion may be an effective future therapy for NAFLD. Disclosure of interest None Declared.

Effect of baseline body mass index (BMI; &lt; 30 kg/m2, ≥30-&lt; 35 kg/m2, and ≥35 kg/m2) on glycaemic response and weight change in patients with type 2 diabetes (T2DM) with baseline HbA1c ≥7.5% after treatment with the once-weekly glucagon-like peptide-1 receptor agonist (GLP-1RA), dulaglutide, and active comparators in five clinical studies (AWARD 1 – 5)

Introduction: We investigated the effect of baseline BMI on treatment with dulaglutide and active comparators in patients with T2DM with baseline HbA1c ≥7.5% (AWARD 1 – 5). The National Institute for Health and Care Excellence (NICE) recommends HbA1c ≥7.5% for initiation of GLP-1RA therapy.

Efficacy and safety of the glucagon-like peptide-1 receptor agonist liraglutide added to insulin therapy in poorly regulated patients with type 1 diabetes—a protocol for a randomised, double-blind, placebo-controlled study: The Lira-1 study

IntroductionIntensive insulin therapy is recommended for the treatment of type 1 diabetes (T1D). Hypoglycaemia and weight gain are the common side effects of insulin treatment and may reduce compliance. In...

Central Functions of Glucagon-like Peptide-1: Roles in Energy Regulation and Neuroprotection

The identification of the glucagon-like peptide-1 receptor in the central nervous system has led to an array of studies exploring the functions of central GLP-1 signalling. Originally identified as a gastrointestinal incretin hormone responsible for the potentiation of insulin secretion following ingestion of nutrients, the role of GLP-1 has been expanded to include specific neural activities. Two distinct actions of GLP-1 receptor activation in the brain have been identified, namely the regulation of appetite via promotion of satiety, as well as anti-inflammatory and anti-apoptotic activity to promote neuronal cell survival. Both of these features are now being exploited clinically, with GLP-1 receptor agonists, initially designed and marketed for the treatment of hyperglycaemia in type 2 diabetes, now being directed towards use in obesity and as potential neuroprotective agents. This review gives a summary of the functional role of GLP-1 in the central nervous system, in terms of promoting satiety, modulating food intake and aiding in the regulation of peripheral glycaemia. In addition, the molecular mechanisms underpinning the beneficial effects of central GLP-1 receptor agonist therapy in protecting against neuronal cell inflammation and death, including neurodegenerative processes, are described.

Retrospective study of adherence to glucagon-like peptide-1 receptor agonist therapy in patients with type 2 diabetes mellitus in the United States.

Greater adherence to medications has been broadly demonstrated to be associated with improved clinical outcomes. However, there is limited real-world evidence on adherence to glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy in patients with type 2 diabetes mellitus (T2DM). This retrospective cohort study used United States administrative claims data to compare adherence to GLP-1RAs in T2DM patients initiating exenatide once weekly (QW), exenatide twice daily (BID), or once-daily liraglutide (initiated therapy = index therapy). Patients were included if they had T2DM, were GLP-1RA-naïve, initiated a GLP-1RA from 02/01/2012-01/31/2013 (date of initiation = index), were ≥18 years at index, and had continuous enrollment for 12 months before (baseline) to 6 months after index (follow-up). Study outcome was index GLP-1RA adherence (proportion of days covered [PDC] during follow-up, dichotomized at ≥80% vs. <80%, and at ≥90% vs. <90%). Multivariable logistic regressions compared adherence between the GLP-1RAs, adjusting for potential confounders. Sensitivity analyses were performed separating liraglutide by dose (1.2 mg/1.8 mg). Study sample included 4,041 exenatide QW, 4,586 exenatide BID, and 14,211 liraglutide (6,641 1.2 mg, 7,570 1.8 mg) patients. Median unadjusted PDC values were 0.783 for exenatide QW, 0.500 exenatide BID, 0.722 liraglutide, 0.761 liraglutide 1.2 mg, and 0.683 liraglutide 1.8 mg. Compared with patients treated with either exenatide BID or liraglutide, patients treated with exenatide QW had a statistically significantly greater multivariable-adjusted odds of achieving adherence of ≥80% (odds ratio vs. exenatide QW (OR) = 0.41 for exenatide BID; 0.80, liraglutide; 0.87, liraglutide 1.2 mg; 0.75, liraglutide 1.8 mg) and ≥90% (OR = 0.31 for exenatide BID; 0.60 liraglutide; 0.66 liraglutide 1.2 mg; 0.56 liraglutide 1.8 mg) (all P < 0.001). Patients initiating exenatide QW had significantly higher adjusted odds of adherence compared with patients initiating other GLP-1RAs. Given differences in adherence across the GLP-1RAs, research correlating these factors with clinical and economic outcomes is warranted.

Prediction of response to GLP-1 receptor agonist therapy in Japanese patients with type 2 diabetes.

BackgroundGlucagon-like peptide-1 (GLP-1) receptor agonists can maintain good glycemic control in some diabetic. Here we compared the clinical characteristics and parameters reflecting glucose metabolism at the time of the initiation of GLP-1 receptor agonist therapy between patients who responded well to therapy and those who did not.MethodsThe records of 43 patients with type 2 diabetes who started receiving GLP-1 receptor agonist therapy during hospitalization were retrospectively reviewed. Glucagon stimulation tests were performed, and patients were started on liraglutide or exenatide therapy. Preprandial blood glucose levels were measured on days 2 and 3 of GLP-1 receptor agonist therapy. We used the Cox proportional hazard model to compare clinical parameters between responders (HbA1c level <8% at more than 3 months after the initiation of treatment) and non-responders (HbA1c level ≥8% at more than 3 months after the initiation of treatment or a switch to insulin therapy at any time).ResultsTwenty-six of the 43 patients were classified as non-responders. At baseline, mean HbA1c levels were 9.9% among responders and 9.7% among non-responders. Compared with treatment with only diet or metformin, the hazard ratio [HR] for non-response was 5.3 (95% confidence interval [CI]: 1.16-24.6, P = 0.03) for insulin therapy and 5.0 (95% CI: 1.13-22.16, P = 0.03) for sulfonylurea therapy. Compared with the lowest tertile, the HRs for non-response in the highest tertile were 3.1 (95% CI: 1.04-8.97, P = 0.04) for the mean preprandial blood glucose level on days 2 and 3 and 3.4 (95% CI: 1.05-11.01, P = 0.04) for the body mass index. The response was not significantly associated with the duration of diabetes or the glucagon stimulation test results. A receiver operating curve analysis showed that the mean preprandial blood glucose level had the highest area under the curve value (=0.72) for the prediction of non-responders.ConclusionsIn patients with poorly controlled diabetes, the response to GLP-1 receptor agonist therapy was significantly associated with the treatment used before the initiation of therapy, the body mass index, and the mean preprandial blood glucose level during the 2 days after the initiation of therapy.

Treatment with a GLP-1 receptor agonist diminishes the decrease in free plasma leptin during maintenance of weight loss.

Background:Recent studies indicate that glucagon-like peptide (GLP)-1 inhibits appetite in part through regulation of soluble leptin receptors. Thus, during weight loss maintenance, GLP-1 receptor agonist (GLP-1RA) administration may inhibit weight loss-induced increases in soluble leptin receptors thereby preserving free leptin levels and preventing weight regain.Methods:In a randomized controlled trial, 52 healthy obese individuals were, after a diet-induced 12% body weight loss, randomized to treatment with or without administration of the GLP-1RA liraglutide (1.2 mg per day). In case of weight gain, low-calorie diet products were allowed to replace up to two meals per day to achieve equal weight maintenance. Glucose tolerance and hormone responses were investigated before and after weight loss and after 52 weeks weight maintenance. Primary end points: increase in soluble leptin receptor plasma levels and decrease in free leptin index after 52 weeks weight loss maintenance.Results:Soluble leptin receptor increase was 59% lower; 2.1±0.7 vs 5.1±0.8 ng ml−1 (−3.0 (95% confidence interval (CI)=−0.5 to −5.5)), P<0.001 and free leptin index decrease was 43% smaller; −62±15 vs −109±20 (−47 (95% CI=−11 to −83)), P<0.05 with administration of GLP-1RA compared with control group. The 12% weight loss was successfully maintained in both the groups with no significant change in weight after 52 weeks follow-up. The GLP-1RA group had greater weight loss during the weight maintenance period (−2.3 kg (95% CI=−0.6 to −4.0)), and had fewer meal replacements per day compared with the control group (minus one meal per day (95% CI=−0.6 to −1)), P<0.001. Fasting glucose was decreased by an additional −0.2±0.1 mmol l−1 in the GLP-1RA group in contrast to the control group, where glucose increased 0.3±0.1 mmol l−1 to the level before weight loss (−0.5mmol l−1 (95% CI=−0.1 to −0.9)), P<0.005. Meal response of peptide PYY3–36 was higher at week 52 in the GLP-1RA group compared with the control group, P<0.05.Conclusions:The weight maintaining effect of GLP-1RAs may be mediated by smaller decrease in free leptin and higher PYY3–36 response. Low dose GLP-1RA therapy maintained 12% weight loss for 1 year and may prevent pre-diabetes in obesity.

Glucagon-like peptide-1 receptor agonists for diabetes mellitus: a role in cardiovascular disease.

Diabetes mellitus, defined as a fasting plasma glucose of ≥126 mg/dL or a glycosylated hemoglobin A1c level (HbA1c) of ≥6.5%, afflicts ≈12.9% of adults in the United States and nearly 285 million adults worldwide.1,2 Diabetes mellitus is a major risk factor for the development of cardiovascular disease, independently conferring a 2-fold excess risk of coronary heart disease and stroke.3 Macrovascular events in diabetes mellitus remain the leading cause of mortality, and the burden of cardiovascular disease attributable to diabetes mellitus has increased over the past decade.4 An increase in the prevalence of obesity has contributed to the rise in diabetes mellitus. Additionally, obesity independently increases the risk of cardiovascular disease in patients with diabetes mellitus.5 Although strict glycemic control unequivocally reduces the microvascular complications of diabetes mellitus, the macrovascular benefits of intensive therapy have been difficult to establish, with conflicting results from large clinical trials.6–9 Multifactorial strategies are recommended to reduce cardiovascular risk in diabetes mellitus through enhanced glycemic control, blood pressure reduction, lipid management, weight loss, and physical activity.10 Unfortunately, despite aggressive interventions for hyperglycemia, <50% of patients achieve standard HbA1c targets with conventional therapy.11 Polypharmacy is required to achieve glycemic control in the majority of patients within 3 years of diagnosis.12 Although combinations of drug classes can synergistically target multiple pathophysiological defects, novel therapies are required to manage diabetes mellitus and mitigate cardiovascular risks. Dipeptidyl-peptidase IV (DPP-IV) inhibitor and glucagon-like peptide-1 (GLP-1) receptor agonist incretin therapies were developed to complement conventional treatment options for diabetes mellitus. Despite promising initial reports of cardioprotective effects, DPP-IV inhibitors have failed to demonstrate improved cardiovascular outcomes in large clinical trials.13–15 Randomized studies to evaluate cardiovascular outcomes associated with GLP-1 receptor agonists are currently underway. This review presents …

PDB136 - Medication use and treatment patterns of glucagon-like peptide-1 receptor agonist therapy in type 2 diabetes mellitus

PDB136 - Medication use and treatment patterns of glucagon-like peptide-1 receptor agonist therapy in type 2 diabetes mellitus

PDB39 - Health care costs among type 2 diabetes mellitus patients initiating glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy

PDB39 - Health care costs among type 2 diabetes mellitus patients initiating glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy

Mody-3: Novel HNF1A Mutation and the Utility of Glucagon-Like Peptide (GLP)-1 Receptor Agonist Therapy

An estimated 1 to 2% of cases of diabetes mellitus have a monogenic basis; however, delayed diagnosis and misdiagnosis as type 1 and 2 diabetes are common. Correctly identifying the molecular basis of an individual's diabetes may significantly alter the management approach to both the patient and his or her relatives. We describe a case of mature onset diabetes of the young (MODY) with sufficient evidence to support the classification of a novel HNF1A (hepatocyte nuclear factor-1-α) mutation as a cause of MODY-3. A 21-year-old Caucasian female presented to our office with a diagnosis of noninsulin-dependent diabetes mellitus (NIDDM) at age 10; glycemia was initially managed with oral antidiabetic (OAD) agents and insulin detemir. The patient reported a strong family history of early-onset NIDDM in both her mother and maternal grandmother, both of whom eventually required insulin therapy to control glycemia. The patient's medical and family history were highly suggestive of maturity-onset diabetes of the young (MODY), and genetic testing was performed. Genetic screening detected a mutation p. Arg200Trp in the HNF1A gene in the patient, her mother, and maternal grandmother, suggesting a diagnosis of MODY-3. This finding resulted in a change of antidiabetic therapy in all 3 patients, including the addition of once-daily liraglutide therapy, which helped improve their glycemic control. Our case report supports the classification of the p. Arg200Trp mutation as a cause of MODY-3. The findings also suggest that glucagon-like peptide-1 (GLP-1) receptor agonist therapy may be of value in managing glycemia in patients with MODY-3.

The impact of improved glycaemic control with GLP-1 receptor agonist therapy on diabetic retinopathy

Rapid improvement in glycaemic control with GLP-1 receptor agonist (RA) therapy has been reported to be associated with significant progression of diabetic retinopathy. This deterioration is transient, and continuing GLP-1 RA treatment is associated with reversal of this phenomenon. Pre-existent maculopathy, higher grade of retinopathy and longer duration of diabetes may be risk factors for persistent deterioration.

Comparison of extended release GLP-1 receptor agonist therapy versus sitagliptin in the management of type 2 diabetes

Exenatide once weekly (EQW), the first glucose-lowering agent for type 2 diabetes that is dosed one time per week, contains exenatide encapsulated in microspheres of a dissolvable matrix, which release active agent slowly and continuously into the circulation following subcutaneous injection. In two direct head-to-head comparisons, EQW resulted in better long-term glucose control, greater reductions in fasting plasma glucose, and more significant weight loss than sitagliptin. In other trials, glucose-lowering effects of EQW compared favorably with those of metformin, pioglitazone, and basal insulin. Patients on EQW exhibited a higher incidence of nausea than those on sitagliptin, although gastrointestinal adverse events occurred primarily during the first 6–8 weeks of therapy and declined thereafter. EQW was also associated with a lower incidence of nausea than two other glucagon-like peptide-1 receptor agonists, exenatide twice daily and liraglutide. Mild hypoglycemic episodes were uncommon with EQW, although risk of hypoglycemia increased in combination with sulfonylureas. When choosing between EQW and a dipeptidyl peptidase-4 (DPP-4) inhibitor, such as sitagliptin, clinicians and patients should consider the differences between the two medications in terms of glucose control (EQW superior to DPP-4 inhibitors), weight control (EQW superior to DPP-4 inhibitors), gastrointestinal tolerability during treatment initiation (EQW inferior to DPP-4 inhibitors), and mode of administration (once-weekly subcutaneous administration versus once-daily oral administration).

Practical Use of Glucagon-Like Peptide-1 Receptor Agonist Therapy in Primary Care

IN BRIEF The glucagon-like peptide-1 (GLP-1) receptor agonist class of medications has distinct benefits and limitations that provide an opportunity to individualize the treatment of patients with type 2 diabetes. Many strategies can be used to improve patient acceptance of and self-management with a GLP-1 receptor agonist.

Was it really pancreatitis from GLP‐1 receptor agonist therapy?

Was it really pancreatitis from GLP‐1 receptor agonist therapy?

Clinical effects of liraglutide on diabetes control in Japanese type 2 diabetes mellitus patients

Our goal was to evaluate liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, in monotherapy and combination therapy for Japanese type 2 diabetes patients. Patients with type 2 diabetes (111 men, 83 women; mean age 57.6 ± 12.6 years) were treated with liraglutide and divided into liraglutide monotherapy (n = 147 patients, group A) and liraglutide–sulfonylurea (SU) combination therapy (n = 47, group B) groups. Changes in clinical parameters after liraglutide administration were evaluated. In both groups, significant decreases in glycosylated hemoglobin (HbA1c) were seen after 12 (group A, 7.01 ± 1.38 vs. 7.72 ± 1.57 %, p < 0.01; group b, 7.83 ± 1.19 vs. 8.44 ± 1.47 %, p < 0.01) and 24 weeks (group A, 7.21 ± 1.45 vs. 7.72 ± 1.57 %, p < 0.01; group B, 7.79 ± 1.22 vs. 8.44 ± 1.47 %, p < 0.01). In group A, body weight decreased significantly from before administration (74.5 ± 19.2 kg) to 12 (73.0 ± 17.8 kg) and 24 (72.8 ± 17.6 kg) (p < 0.01) weeks. In group B, body weight decreased significantly from before administration (71.4 ± 17.4 kg) to 12 weeks (70.9 ± 17.9 kg; p < 0.01). Low-density lipoprotein (LDL) cholesterol decreased significantly in group A from before administration (112.6 ± 34.2 mg/dl) to 12 (107.7 ± 35.0 mg/dl; p < 0.005) and 24 (106.3 ± 26.8 mg/dl; p < 0.05) weeks. In group B, LDL cholesterol decreased significantly from before administration (112.1 ± 24.7 mg/dl) to 12 weeks (99.7 ± 24.7 mg/dl; p < 0.05) only. In both groups, no significant differences in systolic and diastolic blood pressures were observed at 12 and 24 weeks compared with before administration. Adverse events after starting liraglutide occurred in 45 patients (23.2 %), 23 (11.9 %) discontinued treatment. Once-daily liraglutide was well tolerated as monotherapy or combination therapy with SU, demonstrating superior glycemic control with a low rate of hypoglycemia and weight loss.

The Effect of Glucagon-Like Peptide-1 Receptor Agonist Therapy on Body Mass Index in Adolescents With Severe Obesity

Medical treatment options for pediatric obesity remain limited. Glucagon-like peptide-1 (GLP-1) receptor agonists induce weight loss by suppressing appetite and increasing satiety, but few studies have evaluated this therapy as a treatment for obesity. To evaluate the effects of exenatide on body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and cardiometabolic risk factors in adolescents with severe obesity. Three-month, randomized, double-blind, placebo-controlled, multicenter clinical trial followed by a 3-month open-label extension. An academic medical center and an outpatient pediatric endocrinology clinic. A total of 26 adolescents (12-19 years of age) with severe obesity (BMI ≥ 1.2 times the 95th percentile or BMI ≥ 35). All patients received lifestyle modification counseling and were equally randomized to exenatide or placebo injection, twice per day. The primary end point was the mean percent change in BMI measured at baseline and 3 months. Secondary end points included absolute change in BMI, body weight, body fat, blood pressure, hemoglobin A1c, fasting glucose, fasting insulin, and lipids at 3 months. Twenty-two patients completed the trial. Exenatide elicited a greater reduction in percent change in BMI compared with placebo (-2.70% [95% CI, -5.02% to -0.37%]; P = .03). Similar findings were observed for absolute change in BMI (-1.13 [95% CI, -2.03 to -0.24]; P = .02) and body weight (-3.26 kg [95% CI, -5.87 to -0.66 kg]; P = .02). Although not reaching the level of statistical significance, reduction in systolic blood pressure was observed with exenatide. During the open-label extension, BMI was further reduced in those initially randomized to exenatide (cumulative BMI reduction of 4%). These results provide preliminary evidence supporting the feasibility, safety, and efficacy of GLP-1 receptor agonist therapy for the treatment of severe obesity in adolescents. clinicaltrials.gov Identifier: NCT01237197.