Tirzepatide: A Novel, Once-weekly Dual GIP and GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes

Kaneko, Shuji

doi:10.17925/ee.2022.18.1.10

Cited by 16 publications

(10 citation statements)

References 79 publications

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“…The GLP-1 receptor agonists have a wide range of beneficial effects as well as therapeutic potential concerning the cardiovascular system, especially via their inhibition of the development, progression, and rupture of atherosclerotic plaques, as proven by multiple studies [ 34 , 35 ]. It has been proven that any long-acting glucagon-like peptide-1 receptor (GLP-1R) agonist has anti-inflammatory properties similar to those of natural GLP-1 and can therefore help to protect organs like the heart and kidneys [ 36 ].…”

Section: Reviewmentioning

confidence: 99%

“…Furthermore, GIP is found to reduce oxidative stress in human endothelial cells and inflammatory cytokine release in visceral adipose tissue [ 34 ]. Pharmacological concentrations of GIP agonists are more likely to yield protective effects against atherosclerosis [ 36 ]. Nevertheless, further studies are required to obtain absolute clarity regarding the stimulation of GIP in the cardiovascular system [ 34 ].…”

Section: Reviewmentioning

confidence: 99%

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Tirzepatide: A Promising Drug for Type 2 Diabetes and Beyond

Dutta¹,

Kumar²,

Babu³

et al. 2023

Cureus

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Tirzepatide is a promising drug with dual-acting glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor activation that has revolutionized the treatment of type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise. In phase 3 clinical trials (SURPASS 1-5), the dose-dependent efficacy and safety of tirzepatide were assessed by once-weekly subcutaneous injection (5 mg, 10 mg, and 15 mg), as monotherapy or combination therapy, in individuals with T2DM. Tirzepatide has been shown to achieve better glycemic control in terms of glycosylated hemoglobin reduction and improved fasting and postprandial glucose levels as compared to other diabetic medications. Moreover, the studies demonstrate a reduction in body weight (-6.2 to -12.9 kg), and other cardiovascular benefits by altering the lipid profile, reducing blood pressure, and visceral adiposity. Tirzepatide has acceptable side effects and is well tolerated, with a low risk of hypoglycemia. The SURPASS 4 clinical trial has shown positive cardiovascular outcomes in people with T2DM and elevated cardiovascular risk. Additionally, encouraging results from SURMOUNT trials and ongoing SURPASS-CVOT studies will shed more light on cardiovascular safety in the future. In this review, we have summarized the clinical trials and their respective outcomes and highlighted the potential future indications for tirzepatide in the management of obesity, heart failure, and nonalcoholic steatohepatitis.

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Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Tirzepatide: A Promising Drug for Type 2 Diabetes and Beyond

Dutta¹,

Kumar²,

Babu³

et al. 2023

Cureus

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“…In 2022, the FDA approved the use of tirzepatide, a new medication that works as a dual GIP/GLP-1 receptor agonist (also known as "twincretin"), which causes a synergistic effect by enhancing the insulin response and producing a glucagonostatic effect during hyperglycemia [38]. Twincretins have similar effects to GLP-1RAs and, therefore, they also complete 6/8 pieces of the puzzle: the liver, muscle, pancreas (alpha and beta cells), gut, and brain.…”

Section: Antihyperglycemic Agents (Figure 2: Color-coded By Medication)mentioning

confidence: 99%

Perfecting the Puzzle of Pathophysiology: Exploring Combination Therapy in the Treatment of Type 2 Diabetes

Gudoor,

Suits,

Shubrook

2023

Diabetology

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Type 2 diabetes mellitus (T2DM) is a debilitating, lifelong condition with a rising incidence. A wide variety of antihyperglycemic agents are available on the market to treat diabetes. However, the number of patients living with diabetes under suboptimal control remains relatively high. This calls into question whether the application of the current treatment standards is effective and durable to truly manage the disease well. This paper aims to highlight the various classes of antihyperglycemic agents from a pathophysiologic perspective and explore the best possible combination that can have a durable effect on diabetes management. To determine this, an eight-piece pathophysiologic puzzle was created, each piece representing an organ system affected by the disease—liver, pancreas (alpha and beta cells), muscle, adipose tissue, gut, brain, and kidneys. Choosing a combination therapy that is both durable and can effectively address all eight pieces of the puzzle can theoretically create sustainable ameliorating effects. This combination can potentially lead to reduced microvascular and macrovascular complications, as well as work towards creating an ideal long-term, affordable diabetes care plan.

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“…More research is suggested in the available guidance. Fortunately, 20 additional trials [ 17 , 44 , 45 ] aiming to investigate the efficacy of tirzepatide in the clinical setting of T2DM or obesity are ongoing. We can obtain more data to analyze after these trials are completed in the near future.…”

Section: Discussionmentioning

confidence: 99%

Weight loss efficiency and safety of tirzepatide: A Systematic review

Lin

Ling

et al. 2023

PLoS ONE

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Objective Tirzeptide is a novel glucagon-like peptide-1 receptor (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) drug, which shows good efficiency for weight loss. Therefore, we aim to investigate the efficacy and safety of tirzepatide for weight loss in type 2 diabetes mellitus (T2DM) and obesity patients in this meta-analysis study. Methods Cochrane Library, PubMed, Embase, Clinical Trials, and Web of Science were searched from inception to October 5, 2022. All randomized controlled trials (RCTs) were included. The odds ratio (OR) was calculated using fixed-effects or random-effects models by Review Manager 5.3 software. Results In total, ten studies (12 reports) involving 9,873 patients were identified. A significant loss body weight in the tirzepatide group versus the placebo by -9.81 kg (95% CI (-12.09, -7.52), GLP-1 RAs by -1.05 kg (95% CI (-1.48, -0.63), and insulin by -1.93 kg (95% CI (-2.81, -1.05), respectively. In sub-analysis, the body weight of patients was significantly reduced in three tirzepatide doses (5 mg, 10 mg, and 15 mg) when compared with those of the placebo/GLP-1 RA/insulin. In terms of safety, the incidence of any adverse events and adverse events leading to study drug discontinuation was higher in the tirzepatide group, but the incidence of serious adverse events and hypoglycaemia was lower. Additionally, the gastrointestinal adverse events (including diarrhea, nausea, vomiting and decreased appetite) of tirzepatide were higher than those of placebo/basal insulin, but similar to GLP-1 RAs. Conclusion In conclusion, tirzeptide can significantly reduce the weight of T2DM and patient with obesity, and it is a potential therapeutic regimen for weight-loss, but we need to be vigilant about its gastrointestinal reaction.

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Tirzepatide: A Novel, Once-weekly Dual GIP and GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes

Cited by 16 publications

References 79 publications

Tirzepatide: A Promising Drug for Type 2 Diabetes and Beyond

Tirzepatide: A Promising Drug for Type 2 Diabetes and Beyond

Perfecting the Puzzle of Pathophysiology: Exploring Combination Therapy in the Treatment of Type 2 Diabetes

Weight loss efficiency and safety of tirzepatide: A Systematic review

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