Efficacy and Safety of Sitagliptin for the Treatment of New-Onset Diabetes after Renal Transplantation

Boerner, Brian P.; Miles, Clifford D.; Shivaswamy, Vijay

doi:10.1155/2014/617638

Cited by 48 publications

(36 citation statements)

References 31 publications

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“…In the nontransplant setting, DPP-4 inhibitors have a relatively low risk of hypoglycemia, are weight neutral, and can be used safely in patients who have only mild reductions in kidney function or if the dose is adjusted appropriately with more significant chronic kidney disease. Because of these factors, as well as evidence that they do not affect immunosuppressant levels, DPP-4 inhibitors are increasingly used for treatment of PTDM without significant safety concerns identified (179,181,182). Vildagliptin reduced 2-hour plasma glucose on OGTT as well as HbA1c in kidney transplant recipients with impaired glucose toler- Should not be used during acute hospitalization, with 2 GFR, 1 LFTs, CHF, or active, significant infection; and should be held for planned iv contrast procedure Sulfonylureas Efficacy is not well documented in transplant patients.…”

Section: B Outpatient Glucose Managementmentioning

confidence: 99%

“…Retrospective and small random controlled trials of KTX recipients show safety of several DPP-4 inhibitors (8,(181)(182)(183)(184) Reduce dose of all but linagliptin with 2 GFR SGLT-2 inhibitors (dapagliflozin, canagliflozin, empagliflozin)…”

Section: B Outpatient Glucose Managementmentioning

confidence: 99%

“…Importantly, no differences in renal function or immunosuppressant levels were noted, and adverse effects were not different between the two groups. Another DPP-4 inhibitor, sitagliptin, has also been studied for safety and efficacy in a small case series and retrospective study (181,182). Vildagliptin was also reported to be efficacious for pretransplant diabetes or PTDM after heart transplant (184).…”

Section: B Outpatient Glucose Managementmentioning

confidence: 99%

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Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes

Shivaswamy

Boerner

Larsen³

2015

Endocrine Reviews

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238

203

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and VA Nebraska-Western Iowa Health Care System (V.S.), Omaha, Nebraska 68105Post-transplant diabetes mellitus (PTDM) is a frequent consequence of solid organ transplantation. PTDM has been associated with greater mortality and increased infections in different transplant groups using different diagnostic criteria. An international consensus panel recommended a consistent set of guidelines in 2003 based on American Diabetes Association glucose criteria but did not exclude the immediate post-transplant hospitalization when many patients receive large doses of corticosteroids. Greater glucose monitoring during all hospitalizations has revealed significant glucose intolerance in the majority of recipients immediately after transplant. As a result, the international consensus panel reviewed its earlier guidelines and recommended delaying screening and diagnosis of PTDM until the recipient is on stable doses of immunosuppression after discharge from initial transplant hospitalization. The group cautioned that whereas hemoglobin A1C has been adopted as a diagnostic criterion by many, it is not reliable as the sole diabetes screening method during the first year after transplant. Risk factors for PTDM include many of the immunosuppressant medications themselves as well as those for type 2 diabetes. The provider managing diabetes and associated dyslipidemia and hypertension after transplant must be careful of the greater risk for drug-drug interactions and infections with immunosuppressant medications. Treatment goals and therapies must consider the greater risk for fluctuating and reduced kidney function, which can cause hypoglycemia. Research is actively focused on strategies to prevent PTDM, but until strategies are found, it is imperative that immunosuppression regimens are chosen based on their evidence to prolong graft survival, not to avoid PTDM. (Endocrine Reviews 37: 37-61, 2016)

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Section: B Outpatient Glucose Managementmentioning

confidence: 99%

Section: B Outpatient Glucose Managementmentioning

confidence: 99%

Section: B Outpatient Glucose Managementmentioning

confidence: 99%

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Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes

Shivaswamy

Boerner

Larsen³

2015

Endocrine Reviews

Self Cite

238

203

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“…The number of oral drugs available for treatment of hyperglycemia in renal transplant recipients is limited because many recipients often have reduced renal function and because of the potential interactions with immunosuppressive drugs and adverse effects such as hypoglycemic events, which may increase the cardiovascular risk. Efficacy and safety of the dipeptidyl peptidase-4 inhibitors sitagliptin (36,37) and vildagliptin (38,39) have previously been documented in PTDM patients. The insulinotropic and glucagonostatic effects of GLP-1 described in the current study imply that GLP-1 analogues also could be an alternative in the treatment of PTDM.…”

Section: Discussionmentioning

confidence: 99%

GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes

et al. 2016

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OBJECTIVEDevelopment of posttransplantation diabetes (PTDM) is characterized by reduced insulin secretion and sensitivity. We aimed to investigate whether hyperglucagonemia could play a role in PTDM and to examine the insulinotropic and glucagonostatic effects of the incretin hormone glucagon-like peptide 1 (GLP-1) during fasting and hyperglycemic conditions, respectively. RESEARCH DESIGN AND METHODSRenal transplant recipients with (n = 12) and without (n = 12) PTDM underwent two separate experimental days with 3-h intravenous infusions of GLP-1 (0.8 pmol/kg/min) and saline, respectively. After 1 h of infusion, a 2-h hyperglycemic clamp (fasting plasma glucose + 5 mmol/L) was established. Five grams of arginine was given as an intravenous bolus 10 min before termination of the clamp. RESULTSFasting concentrations of glucagon (P = 0.92) and insulin (P = 0.23) were similar between the groups. In PTDM patients, glucose-induced glucagon suppression was significantly less pronounced (maximal suppression from baseline: 43 6 12 vs. 65 6 12%, P < 0.001), while first-and second-phase insulin secretion were significantly lower. The PTDM group also exhibited a significantly lower insulin response to arginine (P = 0.01) but similar glucagon and proinsulin responses compared with control subjects. In the preclamp phase, GLP-1 lowered fasting plasma glucose to the same extent in both groups but reduced glucagon only in PTDM patients. During hyperglycemic clamp, GLP-1 reduced glucagon concentrations and increased first-and second-phase insulin secretion in both groups. CONCLUSIONSPTDM is characterized by reduced glucose-induced insulin secretion and attenuated glucagon suppression during a hyperglycemic clamp. Similar to the case in type 2 diabetes, GLP-1 infusion seems to improve (insulin) or even normalize (glucagon) these pathophysiological defects.In renal transplant recipients, cardiovascular disease persists as the leading cause of premature death (1). Development of posttransplantation diabetes (PTDM) is associated with further increased cardiovascular risk and mortality (2-4). PTDM is primarily believed to be a variant of type 2 diabetes possibly induced by immunosuppressive therapy (5) and/or viral infections (e.g., cytomegalovirus and hepatitis C) that reduce both insulin secretion and insulin sensitivity (6). Importantly, the risk of PTDM can be significantly reduced by proper dosing of the immunosuppressive

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“…Dipeptyl peptidase-4 inhibitors selectively foster insulin secretion without inducing hypoglycemia, which might be advantageous in kidney transplant recipients with NODAT. Dipeptyl peptidase-4 inhibition (vildagliptin, sitagliptin) in kidney transplant recipients with overt NODAT was found to be safe and efficient, providing a novel treatment alternative for this specific form of diabetes [64][65][66] .…”

Section: Post-transplantation Managementmentioning

confidence: 99%

New-onset diabetes mellitus after renal transplantation

Goldmannová¹,

Karásek²,

Krystynik³

et al. 2016

BIOMED PAP

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Background and Aim. Diabetes mellitus is a very common metabolic disease with a rising incidence. It is both a leading cause of chronic renal disease and one of the most serious comorbidities in renal transplant recipients. New-onset diabetes after renal transplantation (NODAT) is associated with poor graft function, higher rates of cardiovascular complications and a poor prognosis. The aim of this paper is to review current knowledge of NODAT including risk factors, diagnosis and management. Methods. A MEDLINE search was performed to retrieve both original and review articles addressing the epidemiology, risk factors, screening and management of NODAT. We also focused on microRNAs as potential biomarkers of NODAT. Results and Conclusion. Understanding the risk factors (both modifiable-e.g. obesity, viruses, and unmodifiable-e.g. age, genetics) may help reduce the incidence and impact of NODAT using pre-and post-transplant management. This can lead to better long-term graft function and general transplant success.

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Efficacy and Safety of Sitagliptin for the Treatment of New-Onset Diabetes after Renal Transplantation

Cited by 48 publications

References 31 publications

Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes

Post-Transplant Diabetes Mellitus: Causes, Treatment, and Impact on Outcomes

GLP-1 Restores Altered Insulin and Glucagon Secretion in Posttransplantation Diabetes

New-onset diabetes mellitus after renal transplantation

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