80-LB: Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist, Is Effective and Safe When Added to Basal Insulin for Treatment of Type 2 Diabetes (SURPASS-5)

Dahl, Dominik; Onishi, Yukiko; Norwood, Paul; Huh, Ruth; Patel, Hiren; Rodríguez, Ángel

doi:10.2337/db21-80-lb

Cited by 14 publications

(26 citation statements)

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“…Tirzepatide provides strong and durable glucose-lowering effects (with data for up to 102 weeks in SURPASS-4), improved β-cell function and insulin sensitivity, dose-dependently reduced weight and improved blood pressure and lipids. [72][73][74][75][76][77] The effects appear to surpass those seen before with other glucose-lowering agents. Furthermore, tirzepatide's safety and tolerability profile appears similar to that of GLP-1 RAs, and therefore reassuring.…”

Section: Perspectives/conclusionmentioning

confidence: 75%

“…In the 26‐week, phase 2b tirzepatide trial, changes in mean body weight ranged from −0.9 to −11.3 kg for tirzepatide compared with −2.7 kg for dulaglutide, and 14%‐71% versus 22% achieved 5% or higher weight loss, and 10% or higher weight loss was obtained by 6%‐39% versus 9%, respectively 43 . In the SURPASS studies, using the efficacy estimand, the highest dose of tirzepatide (15 mg) reduced body weight by 9.5 kg (11.0%) to 12.9 kg (13.9%) 72‐76 . The proportion of individuals losing 5% or more of body weight varied from 54% to 67% for the 5‐mg dose and from 77% to 88% for the 15‐mg dose.…”

Section: Resultsmentioning

confidence: 99%

“…The CV safety of tirzepatide will be studied in the SURPASS‐CVOT trial, which will randomize 12 500 individuals with T2D and will conclude in 2024. Transient elevations in pulse rate and beneficial effects on blood pressure (systolic −5 to −7 mmHg, diastolic −2 to −3 mmHg), and lipids (triglycerides −16% to −25%, HDL‐cholesterol +7%‐11%, LDL‐cholesterol −5% to −8%) have been shown in the SURPASS programme 72‐76 …”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Efficacy and safety of high‐dose glucagon‐like peptide‐1, glucagon‐like peptide‐1/glucose‐dependent insulinotropic peptide, and glucagon‐like peptide‐1/glucagon receptor agonists in type 2 diabetes

Block

Dirinck

Verhaegen

et al. 2022

Diabetes Obesity Metabolism

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Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become agents of choice for people with type 2 diabetes (T2D) with established cardiovascular disease or in highrisk individuals. With currently available GLP-1 RAs, 51%-79% of subjects achieve an HbA1c target of less than 7.0% and 4%-27% lose 10% of body weight, illustrating the need for more potent agents. Three databases (PubMed, Cochrane, Web of Science) were searched using the MESH terms 'glucagon-like peptide-1 receptor agonist', 'glucagon receptor agonist', 'glucose-dependent insulinotropic peptide', 'dual or co-agonist', and 'tirzepatide'. Quality of papers was scored using PRISMA guidelines. Risk of bias was evaluated using the Cochrane assessment tool. An HbA1c target of less than 7.0% was attained by up to 80% with high-dose GLP-1 RAs and up to 97% with tirzepatide, with even up to 62% of people with T2D reaching an HbA1c of less than 5.7%. A body weight loss of 10% or greater was obtained by up to 50% and up to 69% with high-dose GLP-1 RAs or tirzepatide, respectively. The glucose-and weightlowering effects of the GLP-1/glucagon RA cotadutide equal those of liraglutide 1.8 mg.Gastrointestinal side effects of high-dose GLP-1 RAs and co-agonists occurred in 30%-70% of patients, mostly arising within the first 2 weeks of the first dose, being mild or moderate in severity, and transient. The development of high-dose GLP-1 RAs and the dual GLP-1/glucose-dependent insulinotropic peptide RA tirzepatide resulted in increasing numbers of people reaching HbA1c and body weight targets, with up to 62% attaining normoglycaemia with 15-mg tirzepatide. Whether this will also translate to better cardiovascular outcomes and affect treatment guidelines remains to be studied.

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Section: Perspectives/conclusionmentioning

confidence: 75%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Efficacy and safety of high‐dose glucagon‐like peptide‐1, glucagon‐like peptide‐1/glucose‐dependent insulinotropic peptide, and glucagon‐like peptide‐1/glucagon receptor agonists in type 2 diabetes

Block

Dirinck

Verhaegen

et al. 2022

Diabetes Obesity Metabolism

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show abstract

“…In recent phase III clinical trials, tirzepatide showed profound ability to improve body weight and glycemia in patients with obesity and T2D. Depending on the dose (5, 10, or 15 mg QW), 40-52 weeks of treatment with tirzepatide, decreased HbA1c between -1.87 and -2.59%, with 81 -97% of patients achieving a HbA1c <7%, and 23 -62% of patients achieving HbA1c <5.7% (24)(25)(26)(27)196). Serum levels of fasting glucose decreased between 43.6 -67.9 mg/dl while body weight decreased relative baseline between 6.2 -12.9% (24)(25)(26)(27)196).…”

Section: Gipr/glp-1r Dual-agonistsmentioning

confidence: 99%

“…Depending on the dose (5, 10, or 15 mg QW), 40-52 weeks of treatment with tirzepatide, decreased HbA1c between -1.87 and -2.59%, with 81 -97% of patients achieving a HbA1c <7%, and 23 -62% of patients achieving HbA1c <5.7% (24)(25)(26)(27)196). Serum levels of fasting glucose decreased between 43.6 -67.9 mg/dl while body weight decreased relative baseline between 6.2 -12.9% (24)(25)(26)(27)196). After 40 weeks of treatment, 47 -57% of patients treated with tirzepatide 15mg QW decreased body weight >10%, relative to 1% in patients treated with placebo, while 27 -32% of patients decreased body weight >15% (0% in placebo controls) (25,27,196).…”

Section: Gipr/glp-1r Dual-agonistsmentioning

confidence: 99%

Recent Advances in Incretin-Based Pharmacotherapies for the Treatment of Obesity and Diabetes

et al. 2022

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The incretin hormone glucagon-like peptide-1 (GLP-1) has received enormous attention during the past three decades as a therapeutic target for the treatment of obesity and type 2 diabetes. Continuous improvement of the pharmacokinetic profile of GLP-1R agonists, starting from native hormone with a half-life of ~2–3 min to the development of twice daily, daily and even once-weekly drugs highlight the pharmaceutical evolution of GLP-1-based medicines. In contrast to GLP-1, the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) received little attention as a pharmacological target, because of conflicting observations that argue activation or inhibition of the GIP receptor (GIPR) provides beneficial effects on systemic metabolism. Interest in GIPR agonism for the treatment of obesity and diabetes was recently propelled by the clinical success of unimolecular dual-agonists targeting the receptors for GIP and GLP-1, with reported significantly improved body weight and glucose control in patients with obesity and type II diabetes. Here we review the biology and pharmacology of GLP-1 and GIP and discuss recent advances in incretin-based pharmacotherapies.

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The new dual gastric inhibitory peptide/glucagon‐like peptide 1 agonist tirzepatide in type 2 diabetes: Is the future bright?

Papachristou

Popovic

Παπάνας

2021

Diabetes Metabolism Res

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Tirzepatide is a dual gastric inhibitory peptide/glucagon‐like peptide 1 (GIP/GLP‐1) receptor agonist formulated as a synthetic linear peptide, based on the native GIP sequence. It has a prolonged half‐life of 5 days, which enables once‐weekly dosing. Studies have hitherto demonstrated its superiority in achieving optimal glycaemic control and body weight management, as compared with various agents used in the treatment of type 2 diabetes mellitus (T2DM), including GLP‐1 receptor agonists. Thus, it is expected to enrich our therapeutic armamentarium in T2DM. However, further experience, notably longer follow‐up data and information on cardiovascular effects, is still needed.

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80-LB: Tirzepatide, a Dual GIP/GLP-1 Receptor Agonist, Is Effective and Safe When Added to Basal Insulin for Treatment of Type 2 Diabetes (SURPASS-5)

Cited by 14 publications

References 0 publications

Efficacy and safety of high‐dose glucagon‐like peptide‐1, glucagon‐like peptide‐1/glucose‐dependent insulinotropic peptide, and glucagon‐like peptide‐1/glucagon receptor agonists in type 2 diabetes

Efficacy and safety of high‐dose glucagon‐like peptide‐1, glucagon‐like peptide‐1/glucose‐dependent insulinotropic peptide, and glucagon‐like peptide‐1/glucagon receptor agonists in type 2 diabetes

Recent Advances in Incretin-Based Pharmacotherapies for the Treatment of Obesity and Diabetes

The new dual gastric inhibitory peptide/glucagon‐like peptide 1 agonist tirzepatide in type 2 diabetes: Is the future bright?

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