Effects of incretin-based therapeutic agents including tirzepatide on renal outcomes in patients with type 2 diabetes: A systemic review and meta-analysis

Mima, Akira; Gotoda, Masahide; Lee, Rina; Murakami, Ami; Akai, Ryosuke; Lee, Shinji

doi:10.1016/j.metop.2023.100236

Cited by 19 publications

(13 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, sotagliflozin stimulates the release of glucagon‐like peptide‐1 (GLP‐1). The dual action of glucagon and GLP‐1 could prove more advantageous in reducing the risk of kidney‐specific composite outcomes, similar to the superior efficacy demonstrated by trizeptide, a GIP/GLP‐1 dual agonist, compared to a GLP‐1 receptor agonist alone 62,63 …”

Section: Discussionmentioning

confidence: 87%

“…The dual action of glucagon and GLP-1 could prove more advantageous in reducing the risk of kidney-specific composite outcomes, similar to the superior efficacy demonstrated by trizeptide, a GIP/GLP-1 dual agonist, compared to a GLP-1 receptor agonist alone. 62,63 This study had several limitations. First, the study could not access the effect of interventions on the circulating GIP levels.…”

Section: Discussionmentioning

confidence: 95%

See 1 more Smart Citation

Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon‐like peptide 1

Deshmukh,

Kalshetti,

Patil

et al. 2024

Clin Exp Pharma Physio

View full text Add to dashboard Cite

Sotagliflozin is the first dual SGLT1/2 inhibitor antidiabetic drug approved by the US Food and Drug Administration for the management of heart failure. SGLT1/2 inhibition is observed to potentiate the secretion of the incretin hormone, glucagon‐like peptide‐1 (GLP‐1). The current preclinical research sought to investigate the effect of sotagliflozin on the secretion of fat‐regulating peptides such as GLP‐1, glucagon and fibroblast growth factor 21 (FGF21) and their prospective association with sotagliflozin's potential beneficial effects on dyslipidaemia. During an oral fat tolerance test in mice, sotagliflozin substantially increased GLP‐1 and insulin concentrations. Although sotagliflozin alone did not ameliorate postprandial lipemia, its combination with linagliptin (DPP‐IV inhibitor) significantly improved lipid tolerance comparable to orlistat (lipase inhibitor). In a triton‐induced hypertriglyceridemia model, sotagliflozin, along with other medications (fenofibrate, exenatide and linagliptin) reduced fat excursion; however, co‐administration with linagliptin provided no extra advantage. Furthermore, sotagliflozin stimulated glucagon secretion in the alpha TC1.6 cells and healthy mice, which resulted in an increased circulating FGF21 and β‐hydroxybutyrate concentration. Finally, chronic treatment of sotagliflozin in high‐fat diet (HFD)‐fed obese mice resulted in reduced body weight gain, liver triglyceride, cholesterol, interleukin‐6 (IL‐6) and tumour necrosis factor alpha (TNF‐α) levels compared with the placebo group. However, the addition of linagliptin did not provide any additional benefit. In conclusion, sotagliflozin was found to have an effect on GLP‐1 and also stimulate the release of glucagon and FGF21, which are important for regulating fat metabolism. Therefore, sotagliflozin might represent a potential therapeutic approach for the treatment of diabetic dyslipidemia and steatohepatitis.

show abstract

Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 95%

Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon‐like peptide 1

Deshmukh,

Kalshetti,

Patil

et al. 2024

Clin Exp Pharma Physio

View full text Add to dashboard Cite

show abstract

“…Despite benefits being more evident in patients with baseline renal impairment, the protective effects of TZP were also observed in normoalbuminuric and those with glomerular filtration higher than 60 mL/min [69]. To confirm positive results on renal outcomes, the meta-analysis by Mima et al found that TZP remarkably reduced the risk of composite renal outcome by 45% and worsening albuminuria by 62% [70].…”

Section: Tirzepatide and Renal Outcomesmentioning

confidence: 99%

Is Tirzepatide the New Game Changer in Type 2 Diabetes?

Lisco,

Disoteo,

De Geronimo

et al. 2024

Endocrines

View full text Add to dashboard Cite

Background: Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across preclinical and human studies, including data from the SURPASS program. Aims: The goal of this paper was to review the evidence on TZP in terms of glucose control, body weight, and the progression of chronic diabetes-related complications and comorbidities. Results: The mean change in HbA1c ranged from −1.6% to −2.06% over placebo, from −0.29% to −0.92% over each GLP-1RAs, and from −0.7% to −1.09% over basal insulins. In SURPASS-6, TZP was more effective than insulin lispro U100 added to basal insulin in reducing HbA1c levels at the study end (−2.1% vs. −1.1%, respectively). Compared to placebo, TZP induces a significant weight loss: 7.5 (5 mg/week); 11 (10 mg/week); and 12 kg (15 mg/week). Compared to GLP-1RAs, TZP reduces body weight from −1.68 kg to −7.16 kg depending on the dose (5 to 15 mg, respectively). Compared to basal insulin alone rigorously titrated, TZP added onto basal-insulin results in the best strategy for the composite endpoint of improvement of glucose control and weight loss. In SURPASS-6, TZP compared to insulin lispro U100 in add-on to insulin glargine U100 reduced body weight by 9 kg in mean (versus weight gain in basal-bolus users: +3.2 kg). TZP has pleiotropic effects potentially dampening the individual cardiovascular risk, including a reduction in systolic arterial pressure by 4 to 6 mmHg and total cholesterol by 4–6% compared to baseline. A post hoc analysis of SURPASS-4 revealed that TZP, compared to glargine U100, delayed the rate of glomerular filtration decline (−1.4 mL/min vs. −3.6 mL/min, respectively), reduced the rate of urinary albumin excretion (−6.8% vs. +36.9%, respectively), and was associated with a lower occurrence of the composite renal endpoint (HR 0.58 [0.43; 0.80]). Conclusions: Consistent evidence indicates that TZP dramatically changes the clinical course of T2D in different clinical scenarios. The efficacy and safety of TZP on chronic diabetes-related comorbidities and complications seem promising, but ongoing trials will clarify the real benefits.

show abstract

“…However, the risk of ESRD persists despite the efficacy of these agents. Consequently, a significant optimism surrounds tirzepatide, a novel incretin‐based therapeutic agent, for its potential in treating DKD [ 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Tirzepatide Reduces Fat Mass and Provides Good Glycaemic Control in Type 2 Diabetes Patients Undergoing Haemodialysis: A Single‐Centre Retrospective Study

Mima,

Horii

2024

Endocrino Diabet & Metabol

Self Cite

View full text Add to dashboard Cite

ObjectiveTirzepatide is an injectable peptide approved by the US Food and Drug Administration for the treatment of Type 2 diabetes (T2DM). Its weight‐loss effect primarily targets fat reduction; however, such effect on patients with chronic kidney disease (CKD) undergoing haemodialysis (HD) has not been reported.MethodsNine patients with CKD undergoing HD received weekly tirzepatide doses (2.5–7.5 mg) once a week. Evaluations encompassed tirzepatide's impact on dry weight (DW) and body composition assessed at baseline and study conclusion using bioelectrical impedance analysis. This longitudinal study included nine patients, with a median age of 53 years and median HD duration of 4 years.ResultsTirzepatide treatment significantly decreased glycated albumin compared with the value at baseline (22.7 ± 5.4 vs. 18.3 ± 2.5%, p = 0.028, respectively). Significant reductions were observed in DW (−1.0 kg, p = 0.024) and body mass index (−0.6 kg/m2, p = 0.050) following tirzepatide administration. Total fat mass was also reduced, but not significantly (− 2.51% from baseline, p = 0.214). In contrast, skeletal muscle mass was not decreased (−1.02% from baseline, p = 0.722). No serious side effects other than nausea were observed during the study period.ConclusionTirzepatide effectively provides good glycaemic control in T2DM patients undergoing HD, decreasing DW by reducing body fat mass without increasing frailty risk.

show abstract

Effects of incretin-based therapeutic agents including tirzepatide on renal outcomes in patients with type 2 diabetes: A systemic review and meta-analysis

Cited by 19 publications

References 38 publications

Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon‐like peptide 1

Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon‐like peptide 1

Is Tirzepatide the New Game Changer in Type 2 Diabetes?

Tirzepatide Reduces Fat Mass and Provides Good Glycaemic Control in Type 2 Diabetes Patients Undergoing Haemodialysis: A Single‐Centre Retrospective Study

Contact Info

Product

Resources

About