Renal failure and rhabdomyolysis associated with sitagliptin and simvastatin use

Kao, David; Kohrt, Holbrook E.; Kugler, John

doi:10.1111/j.1464-5491.2008.02536.x

Cited by 47 publications

(37 citation statements)

References 4 publications

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“…There has been one case where sitagliptin was associated with worsening of renal function and rhabdomyolysis resulting from increasing circulating levels of simvastatin. This episode may have been the consequence of increasing competition for the renal human organic anion transporter (hOAT3: involved in active renal excretion of both drugs) in an already dysfunctional kidney [91]. The authors suggest that given the high likelihood of sitagliptin being co-administered with statins and other renally active medications, further study of the long-term safety of sitagliptin in renal insufficiency may be warranted.…”

Section: Renal Efficacy and Safetymentioning

confidence: 99%

Renal and Cardiac Effects of DPP-4 Inhibitors from Preclinical Development to Clinical Research

Hocher

Reichetzeder

Alter

2012

Kidney Blood Press Res

132

114

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Inhibitors of type 4 dipeptidyl peptidase (DDP-4) were developed and approved for the oral treatment of type 2 diabetes. Its mode of action is to inhibit the degradation of incretins, such as type 1 glucagon like peptide (GLP-1), and GIP. GLP-1 stimulates glucose-dependent insulin secretion from pancreatic beta-cells and suppresses glucagon release from alpha-cells, thereby improving glucose control. Besides its action on the pancreas type 1 glucagon like peptide has direct effects on the heart, vessels and kidney mainly via the type 1 glucagon like peptide receptor (GLP-1R). Moreover, there are substrates of DPP-4 beyond incretins that have proven renal and cardiovascular effects such as BNP/ANP, NPY, PYY or SDF-1 alpha. Preclinical evidence suggests that DPP-4 inhibitors may be effective in acute and chronic renal failure as well as in cardiac diseases like myocardial infarction and heart failure. Interestingly, large cardiovascular meta-analyses of combined Phase II/III clinical trials with DPP-4 inhibitors point all in the same direction: a potential reduction of cardiovascular events in patients treated with these agents. A pooled analysis of pivotal Phase III, placebo-controlled, registration studies of linagliptin further showed a significant reduction of urinary albumin excretion after 24 weeks of treatment. The observation suggests direct renoprotective effects of DPP-4 inhibition that may go beyond its glucose-lowering potential. Type 4 dipeptidyl peptidase inhibitors have been shown to be very well tolerated in general, but for those excreted via the kidney dose adjustments according to renal function are needed to avoid side effects. In conclusion, the direct cardiac and renal effects seen in preclinical studies as well as meta-analysis of clinical trials may offer additional potentials – beyond improvement of glycemic control - for this newer class of drugs, such as acute kidney failure, chronic kidney failure as well as acute myocardial infarction and heart failure.

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Section: Renal Efficacy and Safetymentioning

confidence: 99%

Renal and Cardiac Effects of DPP-4 Inhibitors from Preclinical Development to Clinical Research

Hocher

Reichetzeder

Alter

2012

Kidney Blood Press Res

132

114

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“…Fortunately, our meta-analysis showed that DPP-4 inhibitors do not increase the risk of hypoglycemia when compared with a placebo or glipizide. One previous study 11 did report renal failure after treatment with DPP-4 inhibitors. However, the long-term safety of DPP-4 inhibitors and their effects on renal toxicity have not been clearly established by large RCTs.…”

Section: Discussionmentioning

confidence: 98%

The efficacy and safety of dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus patients with severe renal impairment: a meta-analysis

et al. 2016

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Aims/introduction Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral antidiabetic agents, and have been increasingly and widely used in the treatment of diabetes mellitus (DM). However, information of DPP-4 inhibitors in type 2 DM patients with severe renal impairment (RI) is limited. Our study aimed to assess the efficacy and safety of DPP-4 inhibitors as compared to placebos or other hypoglycemic drugs in type 2 DM patients with severe RI. Materials and methods A meta-analysis was conducted to examine the literature comparing the effects of DPP-4 inhibitors on hemoglobin A1c (HbA1c) and fasting blood glucose (FBG). Randomized control trials (RCTs) including adults with type 2 DM and severe RI were analyzed. Safety was evaluated based on the percentage of patients who developed hypoglycemia and the occurrence of adverse events (AEs) as well as the incidence of peripheral edema, urinary tract infection, diarrhea, and death.

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“…Another described its association during the concomitant use with an antipsychotic drug [15]. To our knowledge, there have been no reports in the literature describing a direct link between metformin and rhabdomyolysis, although there have been case reports connecting other antidiabetic agents to rhabdomyolysis, such as sitagliptin, rosiglitazone, pioglitazone, and troglitazone [16][17][18][19]. In all of the cases, the described association has occurred in patients who were also taking other medications in addition to the antidiabetic agent of interest, including ones notoriously known to cause rhabdomyolysis, such as statins and fibrates.…”

Section: Discussionmentioning

confidence: 99%

McArdle disease: a “pediatric” disorder presenting in an adult with acute kidney injury

Zhao

Soni

et al. 2017

CEN Case Rep

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Rhabdomyolysis is characterized by the acute breakdown of skeletal muscle, resulting in the release of muscle cell contents, subsequent myoglobinuria, and in severe cases, acute renal failure. A number of etiologies have been identified in acute rhabdomyolysis, in which drugs and trauma account for the majority of cases. One etiological category that is commonly overlooked in the adult population is an underlying genetic defect. This may be challenging to diagnose due to its rarity in the adult demographic and the marked heterogeneity, often requiring a high level of clinical suspicion before investigation is pursued. Once diagnosed, however, appropriate steps can be taken to reduce future episodes of rhabdomyolysis, further renal injury, and other systemic complications. Here, we report a case of an adult patient presenting with acute rhabdomyolysis secondary to McArdle disease, a genetic disease causing defective glycogenolysis. The case highlights the importance of recognizing the potential of undiagnosed ''pediatric'' disorders in adulthood and particularly for underlying genetic causes of rhabdomyolysis.

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Renal failure and rhabdomyolysis associated with sitagliptin and simvastatin use

Cited by 47 publications

References 4 publications

Renal and Cardiac Effects of DPP-4 Inhibitors from Preclinical Development to Clinical Research

Renal and Cardiac Effects of DPP-4 Inhibitors from Preclinical Development to Clinical Research

The efficacy and safety of dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus patients with severe renal impairment: a meta-analysis

McArdle disease: a “pediatric” disorder presenting in an adult with acute kidney injury

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Renal failure and rhabdomyolysis associated with sitagliptin and simvastatin use

Cited by 47 publications

References 4 publications

Renal and Cardiac Effects of DPP-4 Inhibitors  from Preclinical Development to Clinical Research

Renal and Cardiac Effects of DPP-4 Inhibitors  from Preclinical Development to Clinical Research

The efficacy and safety of dipeptidyl peptidase-4 inhibitors for treatment of type 2 diabetes mellitus patients with severe renal impairment: a meta-analysis

McArdle disease: a “pediatric” disorder presenting in an adult with acute kidney injury

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Renal and Cardiac Effects of DPP-4 Inhibitors from Preclinical Development to Clinical Research

Renal and Cardiac Effects of DPP-4 Inhibitors from Preclinical Development to Clinical Research