Safety and tolerability of once‐weekly GLP‐1 receptor agonists in type 2 diabetes

Trujillo, Jennifer M.

doi:10.1111/jcpt.13225

Cited by 73 publications

(50 citation statements)

References 65 publications

(368 reference statements)

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“…As these adverse events can lead to dehydration, GLP-1 RAs should be used with caution in elderly patients or those with renal impairment. Although differences in safety between GLP-1 RAs are not clear, gastrointestinal adverse reactions should be carefully considered when semaglutide is used [27]. In the SUSTAIN-6 study, which evaluated the cardiovascular safety of semaglutide, the incidence of retinopathy complications was high [28].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of semaglutide in glycemic control, body weight management, lipid profiles and other biomarkers among obese type 2 diabetes patients initiated or switched to semaglutide from other GLP-1 receptor agonists

Okamoto

Yokokawa

Nagamine

et al. 2021

J Diabetes Metab Disord

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Purpose Evidence of the efficacy and safety of semaglutide among patients with type 2 diabetes who were initiated on or were switched to semaglutide from other GLP-1 RAs remains limited. The objective of this study was to investigate the short-term effects of switching to semaglutide from other GLP-1 RAs. Methods This retrospective cohort study evaluated patients with type 2 diabetes who were initiated on or were switched to semaglutide due to poor diabetes control with other GLP-1 RAs or other medications, or obesity. HbA1c, body weight, serum creatinine, serum uric acid, parameters of lipid metabolism, and parameters of liver function were measured before and 6 months after administration of semaglutide. Results A total of 50 patients were registered in the study. After switching to semaglutide (n = 43), HbA1c and body weight significantly decreased (p < 0.01, p < 0.01), respectively. The same findings were observed in semaglutide-naïve patients (p = 0.04, p < 0.02) (n = 7). Serum uric acid, total cholesterol, triglycerides, and urinary albumin-creatinine ratio decreased significantly as well (p = 0.04, p = 0.04, p = 0.02, p = 0.04), whereas serum creatinine did not change significantly (p = 0.51). Conclusions Semaglutide showed excellent efficacy, even in patients switched from other GLP-1 RAs. Semaglutide appears to be a promising agent for blood glucose and body weight control in obese type 2 diabetes mellitus patients and could be more potent in treating type 2 diabetes than existing GLP-1 RAs.

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Section: Discussionmentioning

confidence: 99%

Efficacy and safety of semaglutide in glycemic control, body weight management, lipid profiles and other biomarkers among obese type 2 diabetes patients initiated or switched to semaglutide from other GLP-1 receptor agonists

Okamoto

Yokokawa

Nagamine

et al. 2021

J Diabetes Metab Disord

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“…While GLP-1 analogs for treatment of type 2 diabetes cause mild-to-moderate nausea and vomiting in a significant proportion of patients, their benefits in terms of weight loss and improved glycemic control have allowed the class to overcome these tolerability concerns and become one of the most-prescribed classes of type 2 diabetes medications in the US and Europe ( 326 ). Second, up-titration regimens for GLP-1 analogs have mitigated adverse GI side effects, reducing their prevalence and severity in both clinical trials and post-marketing surveillance ( 327 ). FGF21 analogs have not so far employed up-titration, but given the reportedly mild-to-moderate as well as the transient nature of the nausea and diarrhea, such an approach could reasonably be expected to mitigate the GI side effects.…”

Section: Fibroblast Growth Factor 21 Analogs: Clinical Experience In mentioning

confidence: 99%

FGF21: An Emerging Therapeutic Target for Non-Alcoholic Steatohepatitis and Related Metabolic Diseases

2020

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The rising global prevalence of obesity, metabolic syndrome, and type 2 diabetes has driven a sharp increase in non-alcoholic fatty liver disease (NAFLD), characterized by excessive fat accumulation in the liver. Approximately one-sixth of the NAFLD population progresses to non-alcoholic steatohepatitis (NASH) with liver inflammation, hepatocyte injury and cell death, liver fibrosis and cirrhosis. NASH is one of the leading causes of liver transplant, and an increasingly common cause of hepatocellular carcinoma (HCC), underscoring the need for intervention. The complex pathophysiology of NASH, and a predicted prevalence of 3–5% of the adult population worldwide, has prompted drug development programs aimed at multiple targets across all stages of the disease. Currently, there are no approved therapeutics. Liver-related morbidity and mortality are highest in more advanced fibrotic NASH, which has led to an early focus on anti-fibrotic approaches to prevent progression to cirrhosis and HCC. Due to limited clinical efficacy, anti-fibrotic approaches have been superseded by mechanisms that target the underlying driver of NASH pathogenesis, namely steatosis, which drives hepatocyte injury and downstream inflammation and fibrosis. Among this wave of therapeutic mechanisms targeting the underlying pathogenesis of NASH, the hormone fibroblast growth factor 21 (FGF21) holds considerable promise; it decreases liver fat and hepatocyte injury while suppressing inflammation and fibrosis across multiple preclinical studies. In this review, we summarize preclinical and clinical data from studies with FGF21 and FGF21 analogs, in the context of the pathophysiology of NASH and underlying metabolic diseases.

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“…As these adverse events can lead to dehydration, GLP-1 RAs should be used with caution in elderly patients or those with renal impairment. Although differences in safety between GLP-1 RAs are not clear, gastrointestinal adverse reactions should be carefully considered when semaglutide is used [25]. In the SUSTAIN-6 study, which evaluated the cardiovascular safety of semaglutide, the incidence of retinopathy complications was high [26].…”

Section: Discussionmentioning

confidence: 99%

Efficacy and Safety of Semaglutide in Glycemic Control and Body Weight Management Among Obese Type 2 Diabetes Patients Initiated or Switched to Semaglutide From Other GLP-1 Receptor Agonists

Okamoto

Yokokawa

Nagamine

et al. 2021

Preprint

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Background: Evidence of the efficacy and safety of semaglutide among patients with type 2 diabetes who were initiated on or were switched to semaglutide from other GLP-1 RAs remains limited. The objective of this study was to investigate the short-term effects of switching to semaglutide from other GLP-1 RAs.Methods: This retrospective cohort study evaluated patients with type 2 diabetes who were initiated on or were switched to semaglutide due to poor diabetes control with other GLP-1 RAs or other medications, or obesity. HbA1c, body weight, serum creatinine, serum uric acid, parameters of lipid metabolism, and parameters of liver function were measured before and 6 months after administration of semaglutide.Results: A total of 50 patients were registered: 21 men and 29 women, aged 51.3 years. Mean body mass index was 32.2 kg/m2, and serum C-peptide was 2.7mg/mL. After switching to semaglutide (n=43), HbA1c and body weight significantly decreased from 6.72 % to 6.22 % and from 86.5 kg to 82.7 kg, respectively. The same findings were observed in semaglutide-naïve patients (n=7). Serum uric acid, total cholesterol, triglycerides, and urinary albumin-creatinine ratio decreased significantly as well, whereas serum creatinine did not change significantly. Conclusion: Semaglutide showed excellent efficacy, even in patients switched from other GLP-1 RAs. Semaglutide appears to be a promising agent for blood glucose and body weight control in obese type 2 diabetes mellitus patients and could be more potent in treating type 2 diabetes than existing GLP-1 RAs.

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Safety and tolerability of once‐weekly GLP‐1 receptor agonists in type 2 diabetes

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Cited by 73 publications

References 65 publications

Efficacy and safety of semaglutide in glycemic control, body weight management, lipid profiles and other biomarkers among obese type 2 diabetes patients initiated or switched to semaglutide from other GLP-1 receptor agonists

Efficacy and safety of semaglutide in glycemic control, body weight management, lipid profiles and other biomarkers among obese type 2 diabetes patients initiated or switched to semaglutide from other GLP-1 receptor agonists

FGF21: An Emerging Therapeutic Target for Non-Alcoholic Steatohepatitis and Related Metabolic Diseases

Efficacy and Safety of Semaglutide in Glycemic Control and Body Weight Management Among Obese Type 2 Diabetes Patients Initiated or Switched to Semaglutide From Other GLP-1 Receptor Agonists

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