Currently, in the field of metabolic endocrinology, tirzepatide is known as a dual Glucose-dependent insulinotropic polypeptide (GIP) and Glucagon-Like Peptide-1 (GLP-1) receptor agonist (GIP/GLP-1RAs) [1] (Figure 1). In fact, tirzepatide treatment has become widespread worldwide. For treatment of obesity, tirzepatide and concomitant weight-inducing (WI) medications have been studied [2]. They include SURMOUNT-1, -3, -4 trials, which were post hoc analysis of 3 randomized clinical trials (RCTs). The authors have also conducted clinical research on tirzepatide [3,4]. This article will introduce tirzepatide studies published in 2026.

Figure 1: Molecule of Tirzepatide

Revised from Mol Metab18:3-14, 2018.

Tirzepatide has been known for its significant metabolic benefits and weight reduction, but its anti-inflammatory effects have been also present [1]. For the latest report, the cost-effectiveness of tirzepatide at maximum-tolerated-dose (MTD) was studied for the comparison with semaglutide at MTD. They were analyzed for obesity or overweight, from the data of head-to-head phase-3 SURMOUNT-5 trial (cases without T2D) [5]. As a result, tirzepatide with MTD showed less costly and more efficacious in comparison with semaglutide with MTD. For per patient, cost savings was $41,688, QALYs gained 0.506 and positive iNHB was 0.784, suggesting beneficial health from tirzepatide. By prediction from the model, 70 T2D patients will be lower per 1000 cases, associated with 10 fewer CVD patients.

For SURPASS-2 trial, 4 biomarkers of HbA1c, BP, weight and lipid profile were investigated, which are essential factors for preventing diabetic complications [6]. The protocol included 1879 T2D adult cases, and they were randomly divided into 4 groups with tirzepatide (5, 10, 15mg) and semaglutide (1mg). Evaluation was performed at 40 week, and the ratio of successful 3 out of 4 markers were calculated. As a result, attainment ratio was 42%, 53%, 57% in tirzepatide, and 34% in semaglutide, respectively. As to specific therapeutic goals, tirzepatide showed the odd ratio (OR) for achieving standard and intensive target for HbA1c (1.50 for 7%, 1.88 for 6.5%), and weight reduction (2.72 for 10%, 3.86 for 15%). Using the data of SURPASS-5 and 6 studies, clinical effect and safety of tirzepatide for add-on treatment to basal insulin was investigated [7]. When tirzepatide was added to basal insulin glargine, significant reductions in HbA1c, fasting plasma glucose (FPG) and glargine dose were found. These findings suggested clinical efficacy of tirzepatide for diabetic patients with insulin treatment.

Clinical efficacy for major adverse cardiovascular events (MACE) of tirzepatide was studied using data of Researching Evidence with Incretin IN Diabetes (REWIND) (n=2,055) and SURPRASS-CVOT (n=13,165) [8]. SURPRASS-CVOT stands for the Study of Tirzepatide Compared with Dulaglutide on MACE in Participants with Type 2 Diabetes, with cardiovascular outcomes trial (CVOT). As a result, tirzepatide vs placebo showed the association of lower classical MACE-3 (hazard ratio, HR 0.72), death from cardiovascular (CV) cause/HF events (HR 0.70), and all-cause death (HR 0.61). There obtained data were almost consistent for sensitivity analyses, non-adjusted or all REWIND cohort data and also meta-analysis data for GLP-1RAs. In comparison with imputed placebo, tirzepatide showed decreased CV outcomes and all-cause mortality, for T2D cases with atherosclerotic CVD.

A SURPASS J-mono trials were conducted in Japan [9]. Comparative study for 4 groups of tirzepatide (5, 10, 15mg) and dulaglutide 0.75 mg was performed for fatty liver index (FLI), fibrosis-4 index (Fib-4), and liver enzymes (ALT, AST, GGT) for 1 year. As a result, the least square mean changes in FLI was −20.6, −25.6, −31.6, and −3.2, in 4 groups, respectively. In contrast, changes in Fib-4 showed similar in 4 groups. The reduction of FLI showed significantly larger with tirzepatide than dulaglutide from 12-52 weeks. In the study of SURPASS-SWITCH, changing agent from dulaglutide to tirzepatide for T2D adults were investigated [10]. They calculated the improvement of glycemic control and weight reduction. Its aim was to make apparent the effect and safety of weekly agents in subgroups of SURPASS-SWITCH. As a result, tirzepatide showed more reductions of HbA1c and weight at 40 weeks. Greater reduction was found in subgroups of baseline with higher HbA1c and lower BMI.

In 4 groups of tirzepatide (5, 10, 15mg) and semaglutide 1mg, the research for the cost to target analysis was performed [11]. The subjects were 1,845 cases from SURPASS-2 clinical trial. Six composite endpoints included HbA1c (6.5%, <7.0%), weight reduction (≥5%, ≥10%, ≥15%) and avoidance of hypoglycemia. As a result, tirzepatide 5, 10 and 15 mg showed generally lower pharmacy cost per case/year for major endpoints than semaglutide 1 mg. There was only endpoint where semaglutide 1mg showed lower cost, where the achieving target had very strict situation of HbA1c <7.0%, weight loss ≥5%, and no hypoglycemia.

By systematic review, the effect of tirzepatide on the risk of developingT2D among people with obesity or overweight was investigated [12]. When comparing between tirzepatide and semaglutide, the risk of the new-onset diabetes showed hazard ratio (HR) 0.07 for 176 weeks, and HR 0.12 for 193 weeks. Consequently, tirzepatide may show significant effect for preventing T2D for cases with obesity or overweight. Using a network meta-analysis (NMA) method, 127 RCTs (n=58,976) (19,456 T2D, and 39,520 no DM) were analyzed [13]. As a result, tirzepatide, subcutaneous semaglutide, and oral semaglutide showed ≥ 5% weight loss for relative ratio (RR) 2.85 in T2D, and 7.17 without DM. For cases without DM, only tirzepatide and semaglutide_SC were effective for RR 2.99 and 2.75. For cases with T2D, weight reduction with ≥ 10% showed in tirzepatide (14.34), Semaglutide_oral (6.86) and Semaglutide_SC (6.12).

The SUMMIT trial has been a phase 3 study for tirzepatide as GIP/GLP-1RA. It significantly reduced the risk of worsening heart failure (HF) events and cardiovascular death by 38% in patients with HF with preserved ejection fraction (HFpEF) and obesity. From previous reports, clinical effect and cardiovascular function demonstrated several functional and symptomatic improvements [14]. They included decreased circulating markers of myocardial stress, reverse cardiac remodeling on imaging, and fewer worsening HF. Concerning incretin poly-agonists, comparative study was conducted [15]. A comprehensive literature search was performed for RCTs in evaluating tirzepatide, retatrutide, or mazdutide for obese adults. Totally 10 RCTs (n=3236) were analyzed. They showed significantly reduction to placebo for 3 markers, which were body weight -9.4kg, fasting plasma glucose (FPG) -26.89mg/dL. In contrast, higher adverse events were observed for RR 1.13, including gastrointestinal-adverse events (GI-AEs) such as nausea, vomiting, diarrhea and constipation.

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) was formerly known as Non-Alcoholic Fatty Liver Disease (NAFLD). It has been a condition where excess fat accumulates in the liver due to metabolic issues like obesity, diabetes, or high blood pressure, rather than alcohol use. As it affects over 30% of the global population, it is a leading cause of chronic liver disease. It is often reversible through weight reduction and lifestyle modification, but can lead to severe damage if untreated. The research protocol included 2497 cases with male 45%, age 55.6 years, BMI 35.3 kg/m², in average [16]. All these agents relieved improvement of MASH, with significant efficacy in tirzepatide (-34.9%) and resmetirom (-31.5%). Tirzepatide showed significant aminotransferase levels as ALT -30.90%, AST -20.71%. Lanifibranor revealed improvement for lipid profiles as HDL +9.87%, TG -26.9%, but did not show fibrosis improvement with OR 1.26.

As previous concerns, GLP-1RA was likely to cause excessive muscle loss, which may be overestimation. In the experiment of obese mice, GLP-1RA can predominantly reduce body fat alongside a small but significant decrease in lean bone mass (LBM) [17]. Among LBM, reduction of liver mass exceeded change in muscle mass. Thus, for middle-aged mice and human male, GLP-1RA slightly reduce absolute muscle mass, but can positively improve body composition and mobility.

From mentioned above, a variety of data for tirzepatide were introduced from evidence-based medicine (EBM) point of view. Furthermore, our daily QOL and ADL would be crucial and important from psychological and social aspects. To compare once-weekly tirzepatide 10 or 15 mg with placebo, as well as lifestyle questionnaire, 6 RCTs (n=4531) were investigated [18]. Tirzepatide significantly improved physical function, where there were both of short form-36 (SF-36) and also Impact of Weight on Quality of Life-Lite (IWQOL-Lite) clinical trials (CT). Consequently, tirzepatide can contribute QOL, perceived physical capacity, primary care medicine, and anti-aging medicine from now.

In summary, the latest reports have been introduced in this mini-review during 2026. For tirzepatide, acute developing of clinical application and related research have been found so far. We will have to contribute human private wellness, happiness and public welfare associated with useful and beneficial medical evidence and information for effective agent.

Conflict of Interest: The authors declare no conflict of interest.

Funding: There was no funding received for this paper.

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