Effect of glucagon‐like peptide 1 receptor agonists on albuminuria in adult patients with type 2 diabetes mellitus: A systematic review and <scp>meta‐analysis</scp>

Yuan, Daniel; Sharma, Harman; Krishnan, Anirudh; Vangaveti, Venkat; Malabu, Usman H.

doi:10.1111/dom.14776

Cited by 13 publications

(7 citation statements)

References 70 publications

(171 reference statements)

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“…Of importance, this amelioration of the risk for CKD progression has been shown to be mainly driven by the achieved reduction in albuminuria levels 41 . GLP‐1RA treatment in T2DM has also been associated with a significant decrease in albuminuria levels, compared with control, according to a relevant, recent meta‐analysis, although the absolute numeric change seems to be inferior to that achieved with SGLT2 inhibitors and tirzepatide 42 . In total, both antidiabetic drug classes ameliorate albuminuria and decrease the risk for CKD progression in T2DM 43 ; however, SGLT2 inhibitors might be superior to GLP‐1RAs for renal outcomes in patients with T2DM, regardless of albuminuria status at baseline 44 …”

Section: Discussionmentioning

confidence: 99%

“…41 GLP-1RA treatment in T2DM has also been associated with a significant decrease in albuminuria levels, compared with control, according to a relevant, recent meta-analysis, although the absolute numeric change seems to be inferior to that achieved with SGLT2 inhibitors and tirzepatide. 42 In total, both antidiabetic drug classes ameliorate albuminuria and decrease the risk for CKD progression in T2DM 43 ; however, SGLT2 inhibitors might be superior to GLP-1RAs for renal outcomes in patients with T2DM, regardless of albuminuria status at baseline. 44 Thus, tirzepatide seems to be a 'rising star' for the prevention and delaying of CKD and related, surrogate renal outcomes in patients with T2DM, despite the fact that, to date, there is no solid evidence, based on the absence of dedicated renal outcome trials.…”

Section: Discussionmentioning

confidence: 99%

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Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: A systematic review and multilevel meta‐analysis

Karakasis,

Patoulias,

Fragakis

et al. 2023

Diabetes Obesity Metabolism

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AimThe present systematic review aimed to summarize the available evidence from published randomized controlled trials (RCTs) regarding the effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus.Materials and MethodsMedline (via PubMed), Cochrane Library and Scopus were searched until 20 October 2023. Double‐independent study selection, data extraction and quality assessment were performed. Evidence was pooled with a three‐level mixed‐effects meta‐analysis.ResultsIn total, 9533 participants from eight RCTs were analysed. All RCTs had a low risk of bias, according to the Cochrane Collaboration tool (RoB2). Tirzepatide was associated with a significantly greater reduction in urine albumin‐to‐creatinine ratio compared with controls [mean difference (MD) −26.9%; 95% confidence interval (CI) (−34.76, −19.04); p < .001; level of evidence (LoE) moderate]. This effect remained significant in participants with baseline urine albumin‐to‐creatinine ratio ≥30 mg/g [MD −41.42%; 95% CI (−54.38, −28.45); p < .001; LoE moderate]. Based on subgroup analysis, the comparative effect of tirzepatide was significant against placebo and the insulin regimen, whereas no difference was observed compared with semaglutide. The beneficial effect of tirzepatide on albuminuria levels remained significant across all investigated doses (5, 10 and 15 mg), showing a dose‐response relationship. A neutral effect was observed on the estimated glomerular filtration rate [MD 0.39 ml/min/1.73m2; 95% CI (−0.64, 1.42); p = .46; LoE moderate].ConclusionOur findings suggest that tirzepatide probably leads to a significant reduction in albuminuria across all administered doses, while its use is associated with a neutral effect on creatinine clearance as a measure of renal function.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: A systematic review and multilevel meta‐analysis

Karakasis,

Patoulias,

Fragakis

et al. 2023

Diabetes Obesity Metabolism

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“…Secondary analyses from the SUSTAIN-6 trial found that semaglutide reduced the risk of new onset or deterioration of chronic renal disease, as the composite outcome of persisting macroalbuminuria, doubling of serum creatinine, or end-stage renal disease was reduced by 36% [33]. The result of a systematic review and meta-analysis indicates that GLP-1RAs, compared to placebo, provide a statistically relevant improvement in albuminuria by around 16% [58].…”

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

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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.

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“…Renally, GLP-1RAs seem to facilitate natriuresis and mitigate hyperfiltration [104]. According to a recent metaanalysis encompassing at least 22 published articles [106], the use of GLP-1RAs was linked to a noteworthy reduction (16.14%) in albuminuria in patients with type 2 diabetes mellitus compared to a placebo. A novel compound, tirzepatide, which acts as both a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and a GLP-1 RAs, exhibited a significant impact on decreasing albuminuria [107].…”

Section: Glucagon-like Peptide 1 Receptor Agonistmentioning

confidence: 99%

Albuminuria, Forgotten No More: Underlining the Emerging Role in CardioRenal Crosstalk

Romero-González,

Rodríguez-Chitiva,

Cañameras

et al. 2024

JCM

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Kidneys have an amazing ability to adapt to adverse situations, both acute and chronic. In the presence of injury, the kidney is able to activate mechanisms such as autoregulation or glomerular hyperfiltration to maintain the glomerular filtration rate (GFR). While these adaptive mechanisms can occur in physiological situations such as pregnancy or high protein intake, they can also occur as an early manifestation of diseases such as diabetes mellitus or as an adaptive response to nephron loss. Although over-activation of these mechanisms can lead to intraglomerular hypertension and albuminuria, other associated mechanisms related to the activation of inflammasome pathways, including endothelial and tubular damage, and the hemodynamic effects of increased activity of the renin–angiotensin–aldosterone system, among others, are recognized pathways for the development of albuminuria. While the role of albuminuria in the progression of chronic kidney disease (CKD) is well known, there is increasing evidence of its negative association with cardiovascular events. For example, the presence of albuminuria is associated with an increased likelihood of developing heart failure (HF), even in patients with normal GFR, and the role of albuminuria in atherosclerosis has recently been described. Albuminuria is associated with adverse outcomes such as mortality and HF hospitalization. On the other hand, it is increasingly known that the systemic effects of congestion are mainly preceded by increased central venous pressure and transmitted retrogradely to organs such as the liver or kidney. With regard to the latter, a new entity called congestive nephropathy is emerging, in which increased renal venous pressure can lead to albuminuria. Fortunately, the presence of albuminuria is modifiable and new treatments are now available to reverse this common risk factor in the cardiorenal interaction.

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Effect of glucagon‐like peptide 1 receptor agonists on albuminuria in adult patients with type 2 diabetes mellitus: A systematic review and meta‐analysis

Cited by 13 publications

References 70 publications

Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: A systematic review and multilevel meta‐analysis

Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: A systematic review and multilevel meta‐analysis

Is Tirzepatide the New Game Changer in Type 2 Diabetes?

Albuminuria, Forgotten No More: Underlining the Emerging Role in CardioRenal Crosstalk

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