Benefits of Liraglutide Treatment in Overweight and Obese Older Individuals With Prediabetes

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Abstract

OBJECTIVE

The aim was to evaluate the ability of liraglutide to augment weight loss and improve insulin resistance, cardiovascular disease (CVD) risk factors, and inflammation in a high-risk population for type 2 diabetes (T2DM) and CVD.

RESEARCH DESIGN AND METHODS

We randomized 68 older individuals (mean age, 58 ± 8 years) with overweight/obesity and prediabetes to this double-blind study of liraglutide 1.8 mg versus placebo for 14 weeks. All subjects were advised to decrease calorie intake by 500 kcal/day. Peripheral insulin resistance was quantified by measuring the steady-state plasma glucose (SSPG) concentration during the insulin suppression test. Traditional CVD risk factors and inflammatory markers also were assessed.

RESULTS

Eleven out of 35 individuals (31%) assigned to liraglutide discontinued the study compared with 6 out of 33 (18%) assigned to placebo ( P = 0.26). Subjects who continued to use liraglutide ( n = 24) lost twice as much weight as those using placebo ( n = 27; 6.8 vs. 3.3 kg; P < 0.001). Liraglutide-treated subjects also had a significant improvement in SSPG concentration (−3.2 vs. 0.2 mmol/L; P < 0.001) and significantly ( P ≤ 0.04) greater lowering of systolic blood pressure (−8.1 vs. −2.6 mmHg), fasting glucose (−0.5 vs. 0 mmol/L), and triglyceride (−0.4 vs. −0.1 mmol/L) concentration. Inflammatory markers did not differ between the two groups, but pulse increased after liraglutide treatment (6.4 vs. −0.9 bpm; P = 0.001).

CONCLUSIONS

The addition of liraglutide to calorie restriction significantly augmented weight loss and improved insulin resistance, systolic blood pressure, glucose, and triglyceride concentration in this population at high risk for development of T2DM and CVD.

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Most cited references 15

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Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study.

Juan Lin, Chien-An Liu, J. Xiao … (1997)

Individuals with impaired glucose tolerance (IGT) have a high risk of developing NIDDM. The purpose of this study was to determine whether diet and exercise interventions in those with IGT may delay the development of NIDDM, i.e., reduce the incidence of NIDDM, and thereby reduce the overall incidence of diabetic complications, such as cardiovascular, renal, and retinal disease, and the excess mortality attributable to these complications. In 1986, 110,660 men and women from 33 health care clinics in the city of Da Qing, China, were screened for IGT and NIDDM. Of these individuals, 577 were classified (using World Health Organization criteria) as having IGT. Subjects were randomized by clinic into a clinical trial, either to a control group or to one of three active treatment groups: diet only, exercise only, or diet plus exercise. Follow-up evaluation examinations were conducted at 2-year intervals over a 6-year period to identify subjects who developed NIDDM. Cox's proportional hazard analysis was used to determine if the incidence of NIDDM varied by treatment assignment. The cumulative incidence of diabetes at 6 years was 67.7% (95% CI, 59.8-75.2) in the control group compared with 43.8% (95% CI, 35.5-52.3) in the diet group, 41.1% (95% CI, 33.4-49.4) in the exercise group, and 46.0% (95% CI, 37.3-54.7) in the diet-plus-exercise group (P or = 25 kg/m2). In a proportional hazards analysis adjusted for differences in baseline BMI and fasting glucose, the diet, exercise, and diet-plus-exercise interventions were associated with 31% (P < 0.03), 46% (P < 0.0005), and 42% (P < 0.005) reductions in risk of developing diabetes, respectively. Diet and/or exercise interventions led to a significant decrease in the incidence of diabetes over a 6-year period among those with IGT.

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Efficacy and Safety of the Human Glucagon-Like Peptide-1 Analog Liraglutide in Combination With Metformin and Thiazolidinedione in Patients With Type 2 Diabetes (LEAD-4 Met+TZD)

Bernard Zinman, John Gerich, John Buse … (2009)

OBJECTIVE To determine the efficacy and safety of liraglutide (a glucagon-like peptide-1 receptor agonist) when added to metformin and rosiglitazone in type 2 diabetes. RESEARCH DESIGN AND METHODS This 26-week, double-blind, placebo-controlled, parallel-group trial randomized 533 subjects (1:1:1) to once-daily liraglutide (1.2 or 1.8 mg) or liraglutide placebo in combination with metformin (1 g twice daily) and rosiglitazone (4 mg twice daily). Subjects had type 2 diabetes, A1C 7–11% (previous oral antidiabetes drug [OAD] monotherapy ≥3 months) or 7–10% (previous OAD combination therapy ≥3 months), and BMI ≤45 kg/m2. RESULTS Mean A1C values decreased significantly more in the liraglutide groups versus placebo (mean ± SE −1.5 ± 0.1% for both 1.2 and 1.8 mg liraglutide and −0.5 ± 0.1% for placebo). Fasting plasma glucose decreased by 40, 44, and 8 mg/dl for 1.2 and 1.8 mg and placebo, respectively, and 90-min postprandial glucose decreased by 47, 49, and 14 mg/dl, respectively (P < 0.001 for all liraglutide groups vs. placebo). Dose-dependent weight loss occurred with 1.2 and 1.8 mg liraglutide (1.0 ± 0.3 and 2.0 ± 0.3 kg, respectively) (P < 0.0001) compared with weight gain with placebo (0.6 ± 0.3 kg). Systolic blood pressure decreased by 6.7, 5.6, and 1.1 mmHg with 1.2 and 1.8 mg liraglutide and placebo, respectively. Significant increases in C-peptide and homeostasis model assessment of β-cell function and significant decreases in the proinsulin-to-insulin ratio occurred with liraglutide versus placebo. Minor hypoglycemia occurred more frequently with liraglutide, but there was no major hypoglycemia. Gastrointestinal adverse events were more common with liraglutide, but most occurred early and were transient. CONCLUSIONS Liraglutide combined with metformin and a thiazolidinedione is a well-tolerated combination therapy for type 2 diabetes, providing significant improvements in glycemic control.

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Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial.

Michaela Diamant, Luc Van Gaal, Stephen Stranks … (2010)

Diabetes treatments are needed that are convenient, provide effective glycaemic control, and do not cause weight gain. We aimed to test the hypothesis that improvement in haemoglobin A(1c) (HbA(1c)) achieved with once weekly exenatide was superior to that achieved with insulin glargine titrated to glucose targets. In this 26-week, open-label, randomised, parallel study, we compared exenatide with insulin glargine in adults with type 2 diabetes who had suboptimum glycaemic control despite use of maximum tolerated doses of blood-glucose-lowering drugs for 3 months or longer. Patients were randomly assigned to add exenatide (2 mg, once-a-week injection) or insulin glargine (once-daily injection, starting dose 10 IU, target glucose range 4.0-5.5 mmol/L) to their blood-glucose-lowering regimens. Randomisation was with a one-to-one allocation and block size four, stratified according to country and concomitant treatment (70% metformin only; 30% metformin plus sulphonylurea). Participants and clinical investigators were not masked to assignment, but investigators analysing data were. The primary endpoint was change in HbA(1c) from baseline, and analysis of this outcome was by modified intention to treat for all patients who received at least one dose of study drug. This trial is registered at ClinicalTrials.gov, number NCT00641056. 456 patients were randomly allocated to treatment and were included in the modified intention-to-treat analysis (233 exenatide, 223 insulin glargine). Participants who received at least one dose of study drug and for whom baseline and at least one postbaseline measurement of HbA(1c) were available were included in the primary efficacy analysis. Change in HbA(1c) at 26 weeks was greater in patients taking exenatide (n=228; -1.5%, SE 0.05) than in those taking insulin glargine (n=220; -1.3%, 0.06; treatment difference -0.16%, 0.07, 95% CI -0.29 to -0.03). 12 (5%) of 233 patients allocated to exenatide and two (1%) of 223 taking insulin glargine discontinued participation because of adverse events (p=0.012). A planned extension period (up to 2.5 years' duration) is in progress. Once weekly exenatide is an important therapeutic option for patients for whom risk of hypoglycaemia, weight loss, and convenience are particular concerns. Amylin Pharmaceuticals; Eli Lilly and Company. Copyright 2010 Elsevier Ltd. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-ta): Diabetes Care

Journal ID (iso-abbrev): Diabetes Care

Journal ID (hwp): diacare

Journal ID (pmc): dcare

Journal ID (publisher-id): Diabetes Care

Title: Diabetes Care

Publisher: American Diabetes Association

ISSN (Print): 0149-5992

ISSN (Electronic): 1935-5548

Publication date (Print): October 2013

Publication date (Electronic): 14 September 2013

Volume: 36

Issue: 10

Pages: 3276-3282

Affiliations

[1] ¹Department of Medicine, Stanford University School of Medicine, Stanford, California

[2] ²Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, West Hollywood, California

[3] ³Department of Medicine, University of California Los Angeles, Los Angeles, California.

Author notes

Corresponding author: Sun H. Kim, sunhkim@ 123456stanford.edu .

Article

Publisher ID: 0354

DOI: 10.2337/dc13-0354

PMC ID: 3781545

PubMed ID: 23835684

SO-VID: 99bd8fb4-8b4d-4429-88a4-ad816aaf574b

License:

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

History

Date received : 11 February 2013

Date accepted : 25 March 2013

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Pages: 7

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Benefits of Liraglutide Treatment in Overweight and Obese Older Individuals With Prediabetes

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Abstract

OBJECTIVE

RESEARCH DESIGN AND METHODS

RESULTS

CONCLUSIONS

Related collections

GLUT4 biology

Most cited references 15

Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study.

Efficacy and Safety of the Human Glucagon-Like Peptide-1 Analog Liraglutide in Combination With Metformin and Thiazolidinedione in Patients With Type 2 Diabetes (LEAD-4 Met+TZD)

Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial.

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Cited by 34

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