Dataset Information

Tirzepatide Improved Health-Related Quality of Life Compared with Insulin Lispro in Basal Insulin-Treated Adults with Type 2 Diabetes and Inadequate Glycaemic Control: A Randomised Controlled Phase 3b Trial (SURPASS-6).

ABSTRACT:

Introduction

Patients with type 2 diabetes (T2D) who require intensification of basal insulin therapy need treatment options that can improve their health-related quality of life (HRQoL) and translate into better outcomes. These analyses compared patient-reported outcomes (PROs) in patients with T2D receiving tirzepatide or insulin lispro.

Methods

The randomised, open-label, multinational, phase 3b SURPASS-6 trial (NCT04537923) was conducted at 135 medical research centres and hospitals in 15 countries and compared two recommended treatment intensification strategies in people with T2D and inadequate glycaemic control on basal insulin: addition of once-weekly tirzepatide versus addition of prandial insulin lispro. Randomisation was stratified by country, baseline glycated haemoglobin level and metformin use. PROs were measured using the Short Form-36 Health Survey version 2 (SF-36v2) acute form (secondary outcome), EQ-5D-5L, Ability to Perform Physical Activities of Daily Living (APPADL) questionnaire and Impact of Weight on Self-Perceptions (IW-SP) questionnaire (tertiary/exploratory outcomes). PROs were compared for the tirzepatide-pooled dose group (5, 10 and 15 mg) and each tirzepatide dose group versus insulin lispro at 52 weeks using the modified intention-to-treat efficacy analysis set.

Results

Between 19 October 2020 and 01 November 2022, 2267 people were assessed and 1428 participants with T2D were randomised. At 52 weeks, participants in the tirzepatide-pooled group had statistically significant improved scores across all SF-36v2 domains and both component summary scores compared with insulin lispro-treated participants (p < 0.05), with the largest differences observed in the general health, vitality and mental health domains. Statistically significant improved APPADL and IW-SP total scores, as well as EQ visual analogue scale and EQ-5D-5L index scores (after adjustment for baseline scores), were observed in tirzepatide-pooled participants compared with insulin lispro-treated participants.

Conclusions

In adult patients with T2D and inadequate glycaemic control with basal insulin, tirzepatide treatment was associated with greater improvements in HRQoL than prandial insulin therapy in addition to clinically significant improvements in glycaemic and body weight-related parameters.

SUBMITTER: Boye KS

PROVIDER: S-EPMC11330430 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature

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Publications

Tirzepatide Improved Health-Related Quality of Life Compared with Insulin Lispro in Basal Insulin-Treated Adults with Type 2 Diabetes and Inadequate Glycaemic Control: A Randomised Controlled Phase 3b Trial (SURPASS-6).

Boye Kristina Secnik KS Poon Jiat Ling JL Landó Laura Fernández LF Sapin Hélène H Huh Ruth R Wang Mianbo M Williamson Suzanne S Patel Hiren H

Diabetes therapy : research, treatment and education of diabetes and related disorders 20240715 9

<h4>Introduction</h4>Patients with type 2 diabetes (T2D) who require intensification of basal insulin therapy need treatment options that can improve their health-related quality of life (HRQoL) and translate into better outcomes. These analyses compared patient-reported outcomes (PROs) in patients with T2D receiving tirzepatide or insulin lispro.<h4>Methods</h4>The randomised, open-label, multinational, phase 3b SURPASS-6 trial (NCT04537923) was conducted at 135 medical research centres and hos ...[more]

PMID: 39008236

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Project description:ImportanceTirzepatide is a glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist used for the treatment of type 2 diabetes. Efficacy and safety of adding tirzepatide vs prandial insulin to treatment in patients with inadequate glycemic control with basal insulin have not been described.ObjectiveTo assess the efficacy and safety of tirzepatide vs insulin lispro as an adjunctive therapy to insulin glargine.Design, setting, and participantsThis open-label, phase 3b clinical trial was conducted at 135 sites in 15 countries (participants enrolled from October 19, 2020, to November 1, 2022) in 1428 adults with type 2 diabetes taking basal insulin.InterventionsParticipants were randomized (in a 1:1:1:3 ratio) to receive once-weekly subcutaneous injections of tirzepatide (5 mg [n = 243], 10 mg [n = 238], or 15 mg [n = 236]) or prandial thrice-daily insulin lispro (n = 708).Main outcomes and measuresOutcomes included noninferiority of tirzepatide (pooled cohort) vs insulin lispro, both in addition to insulin glargine, in HbA1c change from baseline at week 52 (noninferiority margin, 0.3%). Key secondary end points included change in body weight and percentage of participants achieving hemoglobin A1c (HbA1c) target of less than 7.0%.ResultsAmong 1428 randomized participants (824 [57.7%] women; mean [SD] age, 58.8 [9.7] years; mean [SD] HbA1c, 8.8% [1.0%]), 1304 (91.3%) completed the trial. At week 52, estimated mean change from baseline in HbA1c with tirzepatide (pooled cohort) was -2.1% vs -1.1% with insulin lispro, resulting in mean HbA1c levels of 6.7% vs 7.7% (estimated treatment difference, -0.98% [95% CI, -1.17% to -0.79%]; P < .001); results met noninferiority criteria and statistical superiority was achieved. Estimated mean change from baseline in body weight was -9.0 kg with tirzepatide and 3.2 kg with insulin lispro (estimated treatment difference, -12.2 kg [95% CI, -13.4 to -10.9]). The percentage of participants reaching HbA1c less than 7.0% was 68% (483 of 716) with tirzepatide and 36% (256 of 708) with insulin lispro (odds ratio, 4.2 [95% CI, 3.2-5.5]). The most common adverse events with tirzepatide were mild to moderate gastrointestinal symptoms (nausea: 14%-26%; diarrhea: 11%-15%; vomiting: 5%-13%). Hypoglycemia event rates (blood glucose level <54 mg/dL or severe hypoglycemia) were 0.4 events per patient-year with tirzepatide (pooled) and 4.4 events per patient-year with insulin lispro.Conclusions and relevanceIn people with inadequately controlled type 2 diabetes treated with basal insulin, weekly tirzepatide compared with prandial insulin as an additional treatment with insulin glargine demonstrated reductions in HbA1c and body weight with less hypoglycemia.Trial registrationClinicalTrials.gov Identifier: NCT04537923.

Project description:IntroductionTirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist, provides clinically meaningful improvements in glycaemic control and body weight loss in people with type 2 diabetes. The early efficacy profile of tirzepatide after treatment initiation is of interest. In this exploratory pre-planned analysis, we evaluated the time to achieve glycaemic control and body weight loss thresholds with tirzepatide.MethodsIn two randomised studies, we compared time to achieve HbA1c (< 7.0% and ≤ 6.5%) and weight loss (≥ 5%, SURPASS-2 only) thresholds among people treated with tirzepatide (5, 10, and 15 mg), semaglutide 1 mg in SURPASS-2, and titrated insulin degludec in SURPASS-3. Longitudinal logistic regression models were used to explore the proportion of participants achieving HbA1c and body weight loss thresholds at 4, 12, and 24 weeks. The time to achieve these thresholds was analysed and compared between groups using the Cox proportional-hazards model.ResultsOverall, greater proportions of participants achieved the HbA1c and body weight loss thresholds at 4, 12, and 24 weeks with tirzepatide compared with semaglutide 1 mg and insulin degludec. The median time to achieve HbA1c < 7.0% (8.1 weeks with each tirzepatide dose, 12.0 weeks with semaglutide 1 mg, and 12.1 weeks with insulin degludec) and ≤ 6.5% (12.1, 15.7, and 24.1 weeks, respectively) was faster with tirzepatide than semaglutide 1 mg and insulin degludec. In SURPASS-2, the median time to first achieve a body weight loss of ≥ 5% was faster with tirzepatide 5 mg (16.0 weeks) and 10 and 15 mg (12.4 weeks) than with semaglutide 1 mg (24.0 weeks).ConclusionAnalyses of data from SURPASS-2 and -3 revealed that tirzepatide treatment enabled more people with type 2 diabetes to achieve glycaemic thresholds and these were achieved faster than with semaglutide 1 mg or insulin degludec. Tirzepatide-treated participants also achieved a body weight loss of ≥ 5% significantly faster with tirzepatide than with semaglutide 1 mg.Trial registration numbersNCT03987919; NCT03882970.

Project description:IntroductionThe objective of this work was to assess the association of tirzepatide with changes in insulin sensitivity and beta-cell function in Japanese patients with type 2 diabetes (T2D).MethodsThis was a prespecified analysis of SURPASS J-mono, a multicenter, randomized, double-blind, active-controlled phase 3 study in Japanese participants with T2D. Participants were randomly assigned to receive tirzepatide 5, 10, 15 mg, or dulaglutide 0.75 mg once weekly for 52 weeks. Changes from baseline in homeostatic model assessment (HOMA2) parameters were assessed by a mixed model for repeated measures. Post hoc subgroup analyses were conducted based on high and low baseline C-peptide categories (cutoff: median 1.86 µg/l).ResultsThis analysis included 636 participants (tirzepatide 5 mg: n = 159; 10 mg: n = 158; 15 mg: n = 160; dulaglutide 0.75 mg: n = 159). Fasting insulin and C-peptide levels were significantly reduced from baseline at week 52 at all three tirzepatide doses compared with dulaglutide 0.75 mg (estimated treatment differences [ETDs] for tirzepatide 5, 10, and 15 mg, respectively: insulin, - 22.6%, - 29.8%, and - 31.0%; C-peptide, - 14.2%, - 21.5%, and - 20.7%; p < 0.001 all comparisons). Insulin sensitivity and beta-cell function indices significantly increased in all tirzepatide groups compared with the dulaglutide 0.75-mg group (ETDs for tirzepatide 5, 10, and 15 mg, respectively: HOMA2-%S [insulin], 31.8%, 43.2%, and 49.9%; HOMA2-%S [C-peptide], 24.8%, 33.9%, and 38.2%; HOMA2-%B [insulin], 27.3%, 34.9%, and 40.6%; HOMA2-%B [C-peptide], 31.6%, 40.1%, and 46.7%; p < 0.001 all comparisons). Regardless of baseline C-peptide level, the tirzepatide groups showed significant improvement in glycated hemoglobin at week 52 compared with the dulaglutide group (C-peptide < 1.86 µg/l: - 2.31% to - 2.75% vs. - 1.45%; ≥ 1.86 µg/l: - 2.43% to - 2.89% vs. - 1.12%; p < 0.001).ConclusionsIn these prespecified and post hoc analyses, tirzepatide was associated with improved insulin sensitivity and insulin secretion in Japanese participants with T2D, which may result in reduced fasting insulin levels.ClinicaltrialsGOV: NCT03861052.

Dataset Information

Tirzepatide Improved Health-Related Quality of Life Compared with Insulin Lispro in Basal Insulin-Treated Adults with Type 2 Diabetes and Inadequate Glycaemic Control: A Randomised Controlled Phase 3b Trial (SURPASS-6).

Introduction

Methods

Results

Conclusions

Publications

Tirzepatide Improved Health-Related Quality of Life Compared with Insulin Lispro in Basal Insulin-Treated Adults with Type 2 Diabetes and Inadequate Glycaemic Control: A Randomised Controlled Phase 3b Trial (SURPASS-6).

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