Moderate · human
This updated systematic review and meta-analysis evaluated the efficacy and safety of semaglutide — a GLP-1 receptor agonist — in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and its more severe form, metabolic dysfunction-associated steatohepatitis (MASH). Following PRISMA guidelines and registered on PROSPERO, the authors searched multiple databases through January 2026, ultimately pooling data from 10 studies comprising 1,908 participants. The primary outcomes were histological MASH resolution without worsening of fibrosis and improvement in fibrosis stage; secondary outcomes included liver stiffness and biochemical markers. The meta-analysis found that semaglutide was significantly associated with MASH resolution without fibrosis worsening (OR 3.48; 95% CI: 2.68–4.53). However, the anti-fibrotic effect appeared to be both stage-dependent and time-dependent, with meaningful histological fibrosis reversal observed primarily in non-cirrhotic patients within the durations of the included trials. Improvements in liver stiffness and biochemical markers were also reported. Limitations include the relatively short durations of the constituent trials and heterogeneity across included studies, which may limit generalizability to advanced or cirrhotic disease stages.
British journal of clinical pharmacology · Jun 2026DOI ↗ Animal onlyPreprint
This mouse study investigated the effects of semaglutide, a GLP-1 receptor agonist (GLP-1 RA), administered from preconception through lactation in dams fed either a high-fat diet (HFD) or a standard diet. Researchers assessed metabolic outcomes in both the treated mothers and their offspring, who were weaned onto a standard diet. The study found that semaglutide improved body composition and glucose metabolism in HFD-fed dams during pregnancy, and these benefits persisted approximately 10 weeks after weaning even after treatment was discontinued. Offspring born to HFD-fed, untreated dams showed impaired glucose homeostasis and hepatic steatosis (fatty liver) at 18 weeks of age. These metabolic disturbances were attenuated in offspring whose mothers received semaglutide. Notably, semaglutide treatment did not adversely affect conception rates or fetal viability. The authors conclude that GLP-1 RA therapy during the perinatal period may improve both maternal and offspring metabolic health in an obesity mouse model, and they call for further investigation into GLP-1–based therapies in this context. Key limitations include the exclusive use of a mouse model, limiting direct translation to human pregnancy, and the fact that this appears to be a preprint not yet formally peer-reviewed.
Unknown journal · Jun 2026DOI ↗ Limited · human
This narrative review examined the clinical potential of tirzepatide — a dual agonist of the GLP-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) — specifically in type 1 diabetes mellitus (T1DM), a population distinct from the type 2 diabetes and obesity contexts in which tirzepatide is already established. Researchers searched PubMed/MEDLINE, Scopus, and Google Scholar through March 2026. Across the reviewed studies, tirzepatide was associated with reductions in HbA1c of up to 0.9%, body weight reductions of up to 23.4% (up to 9.0 kg/m² BMI reduction), increases in continuous glucose monitoring time-in-range (TIR) of up to 18.0% (primarily driven by reductions in time above range), and decreases in daily insulin requirements of up to 38 units/day. The authors noted that glycemic and weight benefits appeared to be partly, but not exclusively, mediated by weight loss. Key limitations acknowledged include that most available studies are observational in design, enrolled participants with overweight or obesity, and that randomized controlled trials in T1DM populations are still needed to confirm these findings.
Expert review of clinical pharmacology · Jun 2026DOI ↗ Limited · human
This retrospective federated cohort study used the TriNetX US Collaborative Network to examine whether GLP-1-based therapy (semaglutide or tirzepatide) was associated with lower rates of ICD-10-documented heart failure (HF) or respiratory failure (RF) in non-diabetic adults with rheumatoid arthritis (RA) and obesity (BMI ≥30 kg/m²). Patients were required to have baseline disease-modifying antirheumatic drug (DMARD) use, and those with diabetes or overlapping systemic autoimmune diseases were excluded. After propensity score matching on 68 covariates (1:1), 3,483 patients remained per cohort. The study found that GLP-1-based therapy was associated with a substantially lower hazard of first post-landmark composite HF or RF events during days 91–365. In absolute terms, the primary composite occurred in 0.7% of GLP-1 users versus 1.8% of never-users, corresponding to roughly one fewer event per 100 patients. Heart failure and respiratory failure analyzed separately showed directionally consistent lower hazards, though individual event counts were small. The authors acknowledge that the findings are hypothesis-generating only, are limited by the retrospective, administrative-data design and potential residual confounding, and require prospective validation before informing clinical practice.
Clinical rheumatology · Jun 2026DOI ↗ 🧪 TrialInsufficient
Registered observational trial (completed). This study evaluated whether a 16-week weight-loss program using tirzepatide before elective ventral and incisional hernia surgery could improve surgical readiness and outcomes in patients with obesity. In this retrospective multicenter study, 109 patients entered the program, and 91 completed treatment and underwent surgery. Participants achieved an average weight loss of 13.8%, and all patients who completed the program reached the target weight required for surgery. Compared with a control group of obese patients who underwent hernia repair withou
ClinicalTrials.gov · Jun 2026View trial ↗ 🧪 TrialInsufficient
Registered Phase 2 interventional trial (not yet recruiting). The purpose of the study is to find out if NNC0662-0419 is safe and effective for treating participants living with obesity.
ClinicalTrials.gov · Jun 2026View trial ↗ 🧪 TrialInsufficient
Registered observational trial (enrolling by invitation). The goal of this observational study is to identify the impact of incretin-based obesity medications (e.g., GLP-1 and GLP-1/GIP) on health and economic outcomes among adults who get their health insurance through their employers. The main questions it aims to answer are: 1. Is obesity medication usage is associated with reduced body mass index (BMI) and weight? 2. Is obesity medication usage is associated with reduced utilization of emergency department and inpatient care or obesity-related conditions over time? 3. Is obesity medication
ClinicalTrials.gov · Jun 2026View trial ↗ Limited · human
This prospective, matched controlled study used continuous glucose monitoring (CGM) via FreeStyle Libre to characterize glycaemic patterns during Ramadan 2025 in 54 adults with insulin-treated diabetes. Three matched groups of 18 participants each were compared: type 2 diabetes on basal-bolus insulin alone (BB), type 2 diabetes on basal-bolus insulin plus adjunctive semaglutide or tirzepatide (BB+), and type 1 diabetes on basal-bolus insulin. CGM data were collected over 28 days pre-Ramadan and 29 days during Ramadan. The study found that dysglycaemia was predominantly driven by the post-iftar (meal-breaking) period. The BB group showed marked deterioration in glycaemic control during non-fasting hours. In contrast, the BB+ group demonstrated significantly better time-in-range (74.4% vs. 36.8%), a lower glucose management indicator (6.9% vs. 8.3%), and an approximately 61% reduction in post-iftar glucose excursions, without increased hypoglycaemia or treatment discontinuations. Limitations include a relatively small matched sample size, a single Ramadan observational period, and non-randomized group assignment, which may introduce residual confounding despite matching.
Diabetes research and clinical practice · Jun 2026DOI ↗ 🧪 TrialInsufficient
Registered Phase 3 interventional trial (not yet recruiting). The goal of this clinical trial is to learn the efficacy of combination therapy with tirzepatide, empagliflozin and pioglitazone versus standard therapy in newly diagnosed type 2 diabetes. The main objectives to achieve are: 1. To compare efficacy of the triple combination therapy against standard therapy in achieving type 2 diabetes remission in patients newly diagnosed with T2DM. 2. To compare the effects on β-cell function and glycemic control of the triple combination therapy against standard therapy in patients newly diagnosed
ClinicalTrials.gov · Jun 2026View trial ↗ Limited · humanPreprint
This retrospective, propensity-score matched observational study used de-identified federated U.S. electronic health record (EHR) data to examine real-world associations of semaglutide (n=1,424) and tirzepatide (n=578) use in adults with type 1 diabetes (T1D) compared to 1:1 matched T1D controls (n=2,002) who did not receive these agents, over a study period from 2018–2025. Neither drug is approved for T1D. The study found that both agents were associated with statistically significant reductions in total daily insulin dose, HbA1c, and body weight at 12 and 24 months compared to controls. Greater insulin reductions were observed in semaglutide users who achieved higher weight loss or dose escalation. The pre-vs-post safety analysis identified predominantly gastrointestinal adverse events; DKA, severe hypoglycemia, pancreatitis, and retinopathy did not increase significantly overall, though patients with >30% insulin dose reduction had higher DKA rates. Semaglutide and tirzepatide exposure was associated with lower all-cause mortality and major adverse cardiovascular events versus matched controls. Key limitations include the observational design, EHR data quality constraints, off-label prescribing confounding, and preprint status, meaning findings have not yet undergone peer review.
Unknown journal · Jun 2026DOI ↗ Review
This systematic review examined existing evidence on the use of second-generation incretin analogs — specifically semaglutide (a GLP-1 receptor agonist) and tirzepatide (a dual GLP-1/GIP receptor agonist) — in adults with type 1 diabetes (T1D) or latent autoimmune diabetes in adults (LADA). Researchers screened 3,053 records from six major databases and ClinicalTrials.gov, ultimately identifying 11 eligible publications. These comprised two systematic reviews, one post hoc subgroup analysis, six narrative or consensus reviews, and two LADA case reports. Three key themes emerged from the synthesis: (1) LADA is frequently misdiagnosed or diagnosis is delayed due to its heterogeneous presentation; (2) both tirzepatide and semaglutide show potential benefits in LADA and in certain T1D subtypes, particularly in individuals retaining residual beta-cell function; and (3) existing clinical management frameworks may guide practice while robust trial data are awaited. The authors concluded that current evidence is promising but moderate in quality, and that well-designed, adequately powered randomized controlled trials in clearly defined LADA and T1D populations are needed to establish long-term efficacy and safety. Notable limitations include the small number of eligible studies, the predominance of review-level and narrative publications, and only two primary patient-level reports.
Journal of the American Association of Nurse Practitioners · Jun 2026DOI ↗ 🧪 TrialInsufficient
Registered N/A interventional trial (recruiting). Obese patients exhibit considerable heterogeneity and complex comorbidities, making long-term effective management challenging with monotherapy. While bariatric surgery remains the most effective weight-loss intervention, postoperative weight regain and metabolic deterioration remain significant concerns. glucagon-like peptide-1 receptor agonists (GLP-1RA) offer distinct advantages for weight loss and metabolic control, and their combination with surgery may produce synergistic effects. This study investigates the efficacy and safety of bariatr
ClinicalTrials.gov · Jun 2026View trial ↗ Strong · human
The GLORY-2 trial was a double-blind, placebo-controlled, phase 3 randomized clinical trial evaluating the efficacy and safety of mazdutide — a once-weekly subcutaneous glucagon and GLP-1 receptor dual agonist — for weight reduction in Chinese adults with obesity (BMI ≥30). Conducted across 27 hospitals in China from December 2023 to November 2025, the trial enrolled 461 participants (64% female; mean age ~34 years; mean BMI ~34.3), including 16.1% with type 2 diabetes. Participants were randomized 2:1 to receive 9 mg mazdutide or placebo weekly for 60 weeks alongside lifestyle interventions. The co-primary outcomes were percentage change in body weight and proportion achieving ≥5% weight loss at week 60. The mazdutide group achieved a mean body weight reduction of approximately 16.65% from baseline, compared with 1.50% in the placebo group — a statistically significant between-group difference of approximately 15.15%. Gastrointestinal adverse reactions were more common in the mazdutide group than in the placebo group. Key limitations include the single-ethnicity (Chinese) population, limiting generalizability, and a relatively young mean participant age. The trial was industry-relevant and registered on ClinicalTrials.gov (NCT06164873).
Strong · human
The SYNCHRONIZE-1 trial was a phase 3, double-blind, randomized controlled trial evaluating survodutide — an investigational dual glucagon receptor and GLP-1 receptor agonist — for weight management in adults with obesity (BMI ≥30, or ≥27 with an obesity-related complication) who did not have diabetes. A total of 725 participants were randomized 1:1:1 to one of two dose levels of once-weekly subcutaneous survodutide or placebo, alongside lifestyle counseling, over 76 weeks. The study found that both survodutide groups achieved significantly greater mean body weight reductions compared to placebo (-12.2% and -13.0% versus -5.4%). Approximately 72% of participants in each survodutide group achieved at least 5% body weight reduction, compared to about 46% in the placebo group. The primary analysis used a treatment-regimen estimand accounting for early discontinuations and protocol deviations. Limitations include the relatively short 76-week duration for a chronic condition, the exclusion of people with diabetes, and industry funding by Boehringer Ingelheim. Long-term cardiovascular and safety outcomes remain to be established in ongoing or future trials.
The New England journal of medicine · Jun 2026DOI ↗ Moderate · human
The SYNCHRONIZE-MASLD trial investigated survodutide — a dual glucagon receptor/GLP-1 receptor agonist — in 216 adults with obesity and at-risk metabolic dysfunction-associated steatotic liver disease (MASLD). Participants were randomized 2:1 to once-weekly subcutaneous survodutide 6.0 mg (n=146) or placebo (n=70) for 48 weeks. The trial had two co-primary endpoints: ≥30% reduction in MRI-assessed liver fat content (LFC) and percentage change in body weight from baseline to week 48. Both endpoints were met. The study found that 84.2% of survodutide-treated participants achieved ≥30% LFC reduction versus 24.3% on placebo. Mean body weight decreased by 12.2% with survodutide compared to 1.0% with placebo. The most common adverse events were gastrointestinal in nature, typically mild-to-moderate and concentrated during dose escalation. Key limitations include the relatively short 48-week duration, which precludes conclusions about long-term outcomes such as fibrosis regression or cardiovascular events, a modest sample size, and recruitment restricted to the United States and Spain, limiting generalizability. The study was funded by the manufacturer and used surrogate endpoints rather than hard clinical outcomes.
Nature medicine · Jun 2026DOI ↗ Strong · human
The REIMAGINE 2 trial was a phase 3, double-blind, randomised, placebo- and active-controlled study evaluating the fixed-dose combination of cagrilintide (an amylin receptor agonist) and semaglutide (a GLP-1 receptor agonist), known as CagriSema, in 2,713 adults with inadequately controlled type 2 diabetes and overweight or obesity across 30 countries. Participants were on background metformin with or without an SGLT2 inhibitor and were followed for 68 weeks. The primary endpoint was change in HbA1c from baseline. The study found that the higher-dose CagriSema combination produced a statistically significantly greater reduction in HbA1c compared with semaglutide alone (-1.91 vs. -1.75 percentage points; treatment difference -0.16 percentage points; p=0.0035). Adverse events were more frequent in the combination group (86.9%) than in the semaglutide monotherapy group (81.2%), with gastrointestinal disorders being the most common across active treatment arms. Limitations include the relatively modest absolute difference in HbA1c reduction, a predominantly White study population, and industry funding by Novo Nordisk, which may introduce sponsorship bias.
The lancet. Diabetes & endocrinology · Jun 2026DOI ↗ Moderate · human
REIMAGINE 1 was a randomised, double-blind, placebo-controlled phase 3a trial evaluating once-weekly subcutaneous cagrilintide-semaglutide (CagriSema) — a combination of an amylin receptor agonist (cagrilintide) and a GLP-1 receptor agonist (semaglutide) — in 189 adults with type 2 diabetes inadequately controlled by diet and exercise alone. Conducted across 42 sites in six countries over 40 weeks, participants were assigned to one of two active dose levels or matched placebo. The primary endpoint was change in HbA1c from baseline to week 40. The study found that both active dose levels produced statistically significant and clinically meaningful reductions in HbA1c compared to placebo (estimated treatment differences of −1.7 and −1.4 percentage points for the higher and lower doses, respectively; p<0.0001 for both). Body weight reduction was a notable secondary finding. The safety profile was described as consistent with the GLP-1 receptor agonist class. Key limitations include the relatively small sample size (n=189), short 40-week duration, an early-stage diabetes population not on background glucose-lowering medications, and industry funding from Novo Nordisk, which may introduce bias. These results suggest CagriSema may be a promising therapeutic option for early-stage type 2 diabetes.
The lancet. Diabetes & endocrinology · Jun 2026DOI ↗ Strong · human
The REIMAGINE 3 trial investigated the combination of cagrilintide and semaglutide (CagriSema) as a weekly add-on to daily basal insulin in adults with type 2 diabetes and suboptimal glycaemic control (HbA1c 7.0–10.5%). In this 40-week, double-blind, placebo-controlled phase 3 study conducted across 46 centres in six countries, 274 participants were randomised to one of two active dose combinations (2.4 mg each or 1.0 mg each) or pooled placebo. The primary endpoint—change in HbA1c from baseline to week 40—was significantly greater with both CagriSema doses (–2.33% and –2.10%, respectively) compared with placebo (–0.66%). Both active groups also achieved substantial bodyweight reductions versus placebo, and no additional hypoglycaemia risk was observed. The safety profile was consistent with the GLP-1 receptor agonist class. Limitations include a relatively short 40-week duration, a moderately sized sample, and industry funding by Novo Nordisk. The study authors conclude that CagriSema meaningfully improved glycaemic control when added to basal insulin, without increasing hypoglycaemia risk.
Lancet (London, England) · Jun 2026DOI ↗ Review
This plain-language review provides an educational overview of survodutide, an investigational medication being studied for the treatment of obesity and metabolic dysfunction-associated steatohepatitis (MASH). The review explains how survodutide works mechanistically and summarizes findings from clinical trials, including key health outcomes and reported side effects observed in trial participants. The authors contextualize survodutide within the broader landscape of obesity and MASH as linked metabolic diseases, noting that both conditions involve dysregulation of energy use and storage, and that they frequently co-occur with other metabolic health conditions. Standard-of-care recommendations such as dietary changes and physical activity are acknowledged, alongside pharmacological and surgical interventions. As a review article rather than an original trial, this paper does not generate new primary data; its conclusions are derived from synthesizing existing clinical trial results. Limitations include the non-approved status of survodutide, the inherent scope constraints of a plain-language review format, and the potential for selective reporting of trial findings. The evidence supporting survodutide's effects ultimately depends on the quality and size of the underlying clinical trials referenced, which are not individually appraised within this summary piece.
Therapeutic advances in gastroenterology · Jun 2026DOI ↗ 🧪 TrialInsufficient
Registered expanded_access trial (available). Provide pre-approval single patient expanded access of retatrutide for patients.
ClinicalTrials.gov · Jun 2026View trial ↗