Tirzepatide Once Weekly for the Treatment of Obesity

New England Journal of Medicine, Journal Year: 2022, Volume and Issue: 387(3), P. 205 - 216

Published: June 4, 2022

Obesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy safety of tirzepatide, novel glucose-dependent insulinotropic polypeptide glucagon-like peptide-1 receptor agonist, people with obesity are not known.

Language: Английский

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Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Diabetes Care, Journal Year: 2022, Volume and Issue: 45(11), P. 2753 - 2786

Published: Sept. 23, 2022

The American Diabetes Association and the European for Study of convened a panel to update previous consensus statements on management hyperglycemia in type 2 diabetes adults, published since 2006 last updated 2019. target audience is full spectrum professional health care team providing U.S. Europe. A systematic examination publications 2018 informed new recommendations. These include additional focus social determinants health, system, physical activity behaviors, including sleep. There greater emphasis weight as part holistic approach management. results cardiovascular kidney outcomes trials involving sodium–glucose cotransporter inhibitors glucagon-like peptide 1 receptor agonists, assessment subgroups, inform broader recommendations cardiorenal protection people with at high risk disease. After summary listing recommendations, practical tips implementation are provided.

Language: Английский

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Anti-obesity drug discovery: advances and challenges

Nature Reviews Drug Discovery, Journal Year: 2021, Volume and Issue: 21(3), P. 201 - 223

Published: Nov. 23, 2021

Enormous progress has been made in the last half-century management of diseases closely integrated with excess body weight, such as hypertension, adult-onset diabetes and elevated cholesterol. However, treatment obesity itself proven largely resistant to therapy, anti-obesity medications (AOMs) often delivering insufficient efficacy dubious safety. Here, we provide an overview history AOM development, focusing on lessons learned ongoing obstacles. Recent advances, including increased understanding molecular gut–brain communication, are inspiring pursuit next-generation AOMs that appear capable safely achieving sizeable sustained weight loss. The development therapies loss proved tremendously challenging. Müller et al. drug learned, challenges recent advances field.

Language: Английский

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Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Diabetologia, Journal Year: 2022, Volume and Issue: 65(12), P. 1925 - 1966

Published: Sept. 23, 2022

Language: Английский

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American Association of Clinical Endocrinology Clinical Practice Guideline for the Diagnosis and Management of Nonalcoholic Fatty Liver Disease in Primary Care and Endocrinology Clinical Settings

Endocrine Practice, Journal Year: 2022, Volume and Issue: 28(5), P. 528 - 562

Published: May 1, 2022

Language: Английский

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Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes

JAMA, Journal Year: 2022, Volume and Issue: 327(2), P. 138 - 138

Published: Jan. 11, 2022

InvestigatorsIMPORTANCE Phase 3 trials have not compared semaglutide and liraglutide, glucagon-like peptide-1 analogues available for weight management.OBJECTIVE To compare the efficacy adverse event profiles of once-weekly subcutaneous semaglutide, 2.4 mg, vs once-daily 3.0 mg (both with diet physical activity), in people overweight or obesity.DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label, 68-week, phase 3b trial conducted at 19 US sites from September 2019 (enrollment: 11-November 26) to May 2021 (end follow-up: 11) adults body mass index 30 greater 27 1 more weight-related comorbidities, without diabetes (N = 338).INTERVENTIONS Participants were randomized (3:1:3:1) receive (16-week escalation; n 126), matching placebo, (4-week 127), plus activity.Participants unable tolerate could 1.7 mg; participants liraglutide discontinued treatment restart 4-week titration.Placebo groups pooled (n 85). MAIN OUTCOMES MEASURESThe primary end point was percentage change weight, confirmatory secondary points achievement 10% more, 15% 20% loss, assessed week 68.Semaglutide comparisons active double-blinded against matched placebo groups.Comparisons treatments supportive points. RESULTSOf 338 (mean [SD] age, 49 [13] years; 265 women [78.4%]; mean 104.5 [23.8] kg; index, 37.5 [6.8]), 319 (94.4%) completed trial, 271 (80.2%) treatment.The baseline -15.8% -6.4% (difference, -9.4 [95% CI, -12.0 -6.8]; P < .001);weight -1.9%.Participants had significantly odds achieving loss (70.9% 25.6% [odds ratio, 6.3 {95% 3.5 11.2}], 55.6% 12.0% 7.9 4.1 15.4}], 38.5% 6.0% 8.2 19.1}], respectively; all .001).Proportions discontinuing any reason 13.5% 27.6% liraglutide.Gastrointestinal events reported by 84.1% 82.7% liraglutide.CONCLUSIONS RELEVANCE Among obesity diabetes, added counseling activity, resulted 68 weeks.

Language: Английский

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Triple–Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial

New England Journal of Medicine, Journal Year: 2023, Volume and Issue: 389(6), P. 514 - 526

Published: June 26, 2023

Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors. Its dose-response relationships with respect to side effects, safety, efficacy for treatment obesity are not known.We conducted a phase 2, double-blind, randomized, placebo-controlled trial involving adults who had body-mass index (BMI, weight in kilograms divided by square height meters) 30 or higher BMI 27 less than plus at least one weight-related condition. Participants were randomly assigned 2:1:1:1:1:2:2 ratio receive subcutaneous retatrutide (1 mg, 4 mg [initial dose, 2 mg], 8 12 mg]) placebo once weekly 48 weeks. The primary end point was percentage change body from baseline 24 Secondary points included weeks reduction 5% more, 10% 15% more. Safety also assessed.We enrolled 338 adults, 51.8% whom men. least-squares mean groups -7.2% 1-mg group, -12.9% combined 4-mg -17.3% 8-mg -17.5% 12-mg as compared -1.6% group. At weeks, -8.7% -17.1% -22.8% -24.2% -2.1% more occurred 92%, 75%, 60%, respectively, participants received retatrutide; 100%, 91%, 75% those mg; 93%, 83% 27%, 9%, 2% placebo. most common adverse events gastrointestinal; these dose-related, mostly mild moderate severity, partially mitigated lower starting dose (2 vs. mg). Dose-dependent increases heart rate peaked declined thereafter.In obesity, resulted substantial reductions weight. (Funded Eli Lilly; ClinicalTrials.gov number, NCT04881760.).

Language: Английский

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Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension

Diabetes Obesity and Metabolism, Journal Year: 2022, Volume and Issue: 24(8), P. 1553 - 1564

Published: April 19, 2022

To explore changes in body weight and cardiometabolic risk factors after treatment withdrawal the STEP 1 trial extension.STEP (NCT03548935) randomized 1961 adults with a mass index ≥ 30 kg/m2 (or 27 weight-related co-morbidity) without diabetes to 68 weeks of once-weekly subcutaneous semaglutide 2.4 mg (including 16 dose escalation) or placebo, as an adjunct lifestyle intervention. At week 68, treatments intervention) were discontinued. An off-treatment extension assessed for further year representative subset participants who had completed treatment. This comprised all eligible from any site Canada, Germany UK, sites United States Japan highest main phase recruitment. All analyses exploratory.Extension included 327 participants. From 0 mean loss was 17.3% (SD: 9.3%) 2.0% 6.1%) placebo. Following withdrawal, placebo regained 11.6 7.7) 1.9 4.8) percentage points lost weight, respectively, by 120, resulting net losses 5.6% 8.9%) 0.1% 5.8%), 120. Cardiometabolic improvements seen reverted towards baseline at 120 most variables.One intervention, two-thirds their prior loss, similar variables. Findings confirm chronicity obesity suggest ongoing is required maintain health.

Language: Английский

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Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial

Nature Medicine, Journal Year: 2022, Volume and Issue: 28(10), P. 2083 - 2091

Published: Oct. 1, 2022

Abstract The STEP 5 trial assessed the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo (both plus behavioral intervention) for long-term treatment adults with obesity, or overweight at least one weight-related comorbidity, without diabetes. co-primary endpoints were percentage change in body weight achievement loss ≥5% week 104. Efficacy was among all randomized participants regardless discontinuation rescue intervention. From October 2018 to 1 February 2019, 304 randomly assigned ( n = 152) 152), 92.8% whom completed (attended end-of-trial visit). Most female (236 (77.6%)) white (283 (93.1%)), a mean (s.d.) age 47.3 (11.0) years, mass index 38.5 (6.9) kg m –2 106.0 (22.0) kg. from baseline 104 −15.2% group −2.6% an estimated difference −12.6 %-points (95% confidence interval, −15.3 −9.8; P < 0.0001). More than achieved (77.1% 34.4%; Gastrointestinal adverse events, mostly mild-to-moderate, reported more often (82.2% 53.9%). In summary, (with comorbidity) led substantial, sustained over weeks placebo. NCT03693430

Language: Английский

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SGLT2 inhibitors and GLP-1 receptor agonists: established and emerging indications

The Lancet, Journal Year: 2021, Volume and Issue: 398(10296), P. 262 - 276

Published: June 30, 2021

Language: Английский

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