Dataset Information

Addition of Liraglutide to Insulin in Patients With Type 1 Diabetes: A Randomized Placebo-Controlled Clinical Trial of 12 Weeks.

ABSTRACT:

Objective

To investigate whether addition of three different doses of liraglutide to insulin in patients with type 1 diabetes (T1D) results in significant reduction in glycemia, body weight, and insulin dose.

Research design and methods

We randomized 72 patients (placebo = 18, liraglutide = 54) with T1D to receive placebo and 0.6, 1.2, and 1.8 mg liraglutide daily for 12 weeks.

Results

In the 1.2-mg and 1.8-mg groups, the mean weekly reduction in average blood glucose was -0.55 ± 0.11 mmol/L (10 ± 2 mg/dL) and -0.55 ± 0.05 mmol/L (10 ± 1 mg/dL), respectively (P < 0.0001), while it remained unchanged in the 0.6-mg and placebo groups. In the 1.2-mg group, HbA1c fell significantly (-0.78 ± 15%, -8.5 ± 1.6 mmol/mol, P < 0.01), while it did not in the 1.8-mg group (-0.42 ± 0.15%, -4.6 ± 1.6 mmol/mol, P = 0.39) and 0.6-mg group (-0.26 ± 0.17%, -2.8 ± 1.9 mmol/mol, P = 0.81) vs. the placebo group (-0.3 ± 0.15%, -3.3 ± 1.6 mmol/mol). Glycemic variability was reduced by 5 ± 1% (P < 0.01) in the 1.2-mg group only. Total daily insulin dose fell significantly only in the 1.2-mg and 1.8-mg groups (P < 0.05). There was a 5 ± 1 kg weight loss in the two higher-dose groups (P < 0.05) and by 2.7 ± 0.6 kg (P < 0.01) in the 0.6-mg group vs. none in the placebo group. In the 1.2- and 1.8-mg groups, postprandial plasma glucagon concentration fell by 72 ± 12% and 47 ± 12%, respectively (P < 0.05). Liraglutide led to higher gastrointestinal adverse events (P < 0.05) and ≤1% increases (not significant) in percent time spent in hypoglycemia (<55 mg/dL, 3.05 mmol/L).

Conclusions

Addition of 1.2 mg and 1.8 mg liraglutide to insulin over a 12-week period in overweight and obese patients with T1D results in modest reductions of weekly mean glucose levels with significant weight loss, small insulin dose reductions, and frequent gastrointestinal side effects. These findings do not justify the use of liraglutide in all patients with T1D.

SUBMITTER: Kuhadiya ND

PROVIDER: S-EPMC5864130 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Publications

Addition of Liraglutide to Insulin in Patients With Type 1 Diabetes: A Randomized Placebo-Controlled Clinical Trial of 12 Weeks.

Kuhadiya Nitesh D ND Dhindsa Sandeep S Ghanim Husam H Mehta Aditya A Makdissi Antoine A Batra Manav M Sandhu Sartaj S Hejna Jeanne J Green Kelly K Bellini Natalie N Yang Min M Chaudhuri Ajay A Dandona Paresh P

Diabetes care 20160405 6

<h4>Objective</h4>To investigate whether addition of three different doses of liraglutide to insulin in patients with type 1 diabetes (T1D) results in significant reduction in glycemia, body weight, and insulin dose.<h4>Research design and methods</h4>We randomized 72 patients (placebo = 18, liraglutide = 54) with T1D to receive placebo and 0.6, 1.2, and 1.8 mg liraglutide daily for 12 weeks.<h4>Results</h4>In the 1.2-mg and 1.8-mg groups, the mean weekly reduction in average blood glucose was - ...[more]

PMID: 27208343

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Project description:BackgroundLiraglutide is an antidiabetic agent with cardioprotective effect. The purpose of this study is to test efficacy of liraglutide to improve diabetic cardiomyopathy in patients with diabetes mellitus type 2 (DM2) without cardiovascular disease.MethodsPatients with DM2 were randomly assigned to receive liraglutide 1.8 mg/day or placebo in this double-blind trial of 26 weeks. Primary outcome measures were LV diastolic function (early (E) and late (A) transmitral peak flow rate, E/A ratio, early deceleration peak (Edec), early peak mitral annular septal tissue velocity (Ea) and estimated LV filling pressure (E/Ea), and systolic function (stroke volume, ejection fraction, cardiac output, cardiac index and peak ejection rate) assessed with CMR. Intention-to-treat analysis of between-group differences was performed using ANCOVA. Mean estimated treatment differences (95% confidence intervals) are reported.Results23 patients were randomized to liraglutide and 26 to placebo. As compared with placebo, liraglutide significantly reduced E (- 56 mL/s (- 91 to - 21)), E/A ratio (- 0.17 (- 0.27 to - 0.06)), Edec (- 0.9 mL/s2 * 10-3 (- 1.3 to - 0.2)) and E/Ea (- 1.8 (- 3.0 to - 0.6)), without affecting A (3 mL/s (- 35 to 41)) and Ea (0.4 cm/s (- 0.9 to 1.4)). Liraglutide reduced stroke volume (- 9 mL (- 16 to - 2)) and ejection fraction (- 3% (- 6 to - 0.1)), but did not change cardiac output (- 0.4 L/min (- 0.9 to 0.2)), cardiac index (- 0.1 L/min/m2 (- 0.4 to 0.1)) and peak ejection rate (- 46 mL/s (- 95 to 3)).ConclusionsLiraglutide reduced early LV diastolic filling and LV filling pressure, thereby unloading the left ventricle. LV systolic function reduced and remained within normal range. Future studies are needed to investigate if liraglutide-induced left ventricular unloading slows progression of diabetic cardiomyopathy into symptomatic stages. Trial registration ClinicalTrials.gov: NCT01761318.

Project description:The aim of the study was to compare the efficacy and safety of liraglutide in type 2 diabetes mellitus vs placebo and insulin glargine (A21Gly,B31Arg,B32Arg human insulin), all in combination with metformin and glimepiride.This randomised (using a telephone or web-based randomisation system), parallel-group, controlled 26 week trial of 581 patients with type 2 diabetes mellitus on prior monotherapy (HbA(1c) 7.5-10%) and combination therapy (7.0-10%) was conducted in 107 centres in 17 countries. The primary endpoint was HbA(1c). Patients were randomised (2:1:2) to liraglutide 1.8 mg once daily (n = 232), liraglutide placebo (n = 115) and open-label insulin glargine (n = 234), all in combination with metformin (1 g twice daily) and glimepiride (4 mg once daily). Investigators, participants and study monitors were blinded to the treatment status of the liraglutide and placebo groups at all times.The number of patients analysed as intention to treat were: liraglutide n = 230, placebo n = 114, insulin glargine n = 232. Liraglutide reduced HbA(1c) significantly vs glargine (1.33% vs 1.09%; -0.24% difference, 95% CI 0.08, 0.39; p = 0.0015) and placebo (-1.09% difference, 95% CI 0.90, 1.28; p < 0.0001). There was greater weight loss with liraglutide vs placebo (treatment difference -1.39 kg, 95% CI 2.10, 0.69; p = 0.0001), and vs glargine (treatment difference -3.43 kg, 95% CI 4.00, 2.86; p < 0.0001). Liraglutide reduced systolic BP (-4.0 mmHg) vs glargine (+0.5 mmHg; -4.5 mmHg difference, 95% CI 6.8, -2.2; p = 0.0001) but not vs placebo (p = 0.0791). Rates of hypoglycaemic episodes (major, minor and symptoms only, respectively) were 0.06, 1.2 and 1.0 events/patient/year, respectively, in the liraglutide group (vs 0, 1.3, 1.8 and 0, 1.0, 0.5 with glargine and placebo, respectively). A slightly higher number of adverse events (including nausea at 14%) were reported with liraglutide, but only 9.8% of participants in the group receiving liraglutide developed anti-liraglutide antibodies.Liraglutide added to metformin and sulfonylurea produced significant improvement in glycaemic control and bodyweight compared with placebo and insulin glargine. The difference vs insulin glargine in HbA(1c) was within the predefined non-inferiority margin.ClinicalTrials.gov NCT00331851.The study was funded by Novo Nordisk A/S.

Dataset Information

Addition of Liraglutide to Insulin in Patients With Type 1 Diabetes: A Randomized Placebo-Controlled Clinical Trial of 12 Weeks.

Objective

Research design and methods

Results

Conclusions

Publications

Addition of Liraglutide to Insulin in Patients With Type 1 Diabetes: A Randomized Placebo-Controlled Clinical Trial of 12 Weeks.

Similar Datasets

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