Incretin Therapies in the Management of Patients with Type 2 Diabetes Mellitus and Renal Impairment

Dejager, S.; Schweizer, Anja

doi:10.3810/hp.2012.04.965

Cited by 20 publications

(25 citation statements)

References 96 publications

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“…In addition, hypoglycemia poses greater threat to patient safety in CKD, as suggested by a large retrospective analysis of patients cared for at the Veterans Health Administration in which hypoglycemia was associated with excessive mortality 17. SU use sharply increases the risk of hypoglycemia, a risk which further rises with older age and decreasing RF 33. Besides the hypoglycemic risk, SU users, compared with metformin, were shown to be at increased risk for decline in eGFR, diagnosis of ESRD, or death, in a retrospective cohort of 93,577 diabetic patients with baseline normal RF from the national Veterans Administration database 34.…”

Section: Discussionmentioning

confidence: 99%

“…DPP4-i improve glycemic control in a glucose-dependent manner and are associated with a low incidence of hypoglycemia, a distinct benefit in this RI population at high risk, and most are now approved for use in patients with moderate or severe RI 33. Data assessing the use of these novel agents in RI patients have been recently published, with vildagliptin42,43 (including in severe RI44 and in elderly patients45), as well as with sitagliptin,46,47 saxagliptin,48 and linagliptin 49…”

Section: Discussionmentioning

confidence: 99%

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How are patients with type 2 diabetes and renal disease monitored and managed? Insights from the observational OREDIA study

Penfornis¹,

Blicklé²,

Fiquet³

et al. 2014

VHRM

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Background and aimChronic kidney disease (CKD) is frequent in type 2 diabetes mellitus (T2DM), and therapeutic management of diabetes is more challenging in patients with renal impairment (RI). The place of metformin is of particular interest since most scientific societies now recommend using half the dosage in moderate RI and abstaining from use in severe RI, while the classic contraindication with RI has not been removed from the label. This study aimed to assess the therapeutic management, in particular the use of metformin, of T2DM patients with CKD in real life.MethodsThis was a French cross-sectional observational study: 3,704 patients with T2DM diagnosed for over 1 year and pharmacologically treated were recruited in two cohorts (two-thirds were considered to have renal disease [CKD patients] and one-third were not [non-CKD patients]) by 968 physicians (81% general practitioners) in 2012.ResultsCKD versus non-CKD patients were significantly older with longer diabetes history, more diabetic complications, and less strict glycemic control (mean glycated hemoglobin [HbA1c] 7.5% versus 7.1%; 25% of CKD patients had HbA1c ≥8% versus 15% of non-CKD patients). Fifteen percent of CKD patients had severe RI, and 66% moderate RI. Therapeutic management of T2DM was clearly distinct in CKD, with less use of metformin (62% versus 86%) but at similar mean daily doses (~2 g/d). Of patients with severe RI, 33% were still treated with metformin, at similar doses. For other oral anti-diabetics, a distinct pattern of use was seen across renal function (RF): use of sulfonylureas (32%, 31%, and 20% in normal RF, moderate RI, and severe RI, respectively) and DPP4-i (dipeptidyl peptidase-4 inhibitors) (41%, 36%, and 25%, respectively) decreased with RF, while that of glinides increased (8%, 14%, and 18%, respectively). CKD patients were more frequently treated with insulin (40% versus 16% of non-CKD patients), and use of insulin increased with deterioration of RF (19%, 39%, and 61% of patients with normal RF, moderate RI, and severe RI, respectively). Treatment was modified at the end of the study-visit in 34% of CKD patients, primarily to stop or reduce metformin. However, metformin was stopped in only 40% of the severe RI patients.ConclusionDespite a fairly good detection of CKD in patients with T2DM, RI was insufficiently taken into account for adjusting anti-diabetic treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

How are patients with type 2 diabetes and renal disease monitored and managed? Insights from the observational OREDIA study

Penfornis¹,

Blicklé²,

Fiquet³

et al. 2014

VHRM

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“…Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, has been shown to be effective and well tolerated with a low incidence of hypoglycemia in clinical trials up to 2 years across disease stages [20], including in higher-risk populations with more severe consequences of hypoglycemia, such as in elderly patients aged ≥75 years [21], patients with renal impairment [22], and insulin-treated patients [23]. The risk of severe hypoglycemia has been shown to be significantly reduced with vildagliptin versus SUs [24, 25].…”

Section: Introductionmentioning

confidence: 99%

Experience with Vildagliptin in Type 2 Diabetic Patients Fasting During Ramadan in France: Insights from the VERDI Study

et al. 2013

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AimTo assess in real life the rate of hypoglycemia during Ramadan in patients with type 2 diabetes (T2DM) in France, according to their ongoing dual therapy of metformin-vildagliptin or metformin-sulfonylurea/glinide (IS).MethodsProspective, non-interventional study with 2 visits (within 8 weeks before and 6 weeks after the end of Ramadan 2012). Study diaries were not used to collect events or record values of glucose monitoring. One hundred and ninety-eight patients on stable oral dual therapy for ≥2 months and with glycosylated hemoglobin (HbA1c) ≤8.0% were recruited by 62 centers: 83 in the IS cohort and 115 in the vildagliptin cohort.ResultsApproximately 90% of patients were from Maghreb. The two cohorts were well balanced: 60% men, mean age 59 years, BMI 28 kg/m2, metformin dose ~2,000 mg/day, and HbA1c 7.2%. Distinct therapeutic management was planned in view of Ramadan with drug-adaptation intended in 61.4% of IS and 18.3% of vildagliptin patients. Hypoglycemia was reported in 37% of IS and 34% of vildagliptin patients; episodes declared as confirmed in 30.8% and 23.5%, respectively, and episodes documented as adverse event (AE) in 17.9% (22 episodes) and 7.5% (13 episodes), respectively (P = 0.025). Severe episodes were reported in 3.9% of IS and 1.7% of vildagliptin patients. 10.4% of IS and 2.6% of vildagliptin patients reported severe episodes and/or unscheduled medical visits due to hypoglycemia (P = 0.029). Glycemic control remained stable in both cohorts. Compliance with fasting was high, as well as adherence to drug with ≥5 missed-dose for 15.4% of IS and 8.5% of vildagliptin patients.ConclusionAlthough the overall frequency of malaise suggestive of hypoglycemia was high, which would be expected with prolonged fasting in a well-controlled T2DM population during hot summer days, the incidence of more severe and better-documented episodes (AE, severe event, event leading to unscheduled medical visit) were much lower, with consistently less events with vildagliptin therapy.

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“…As demonstrated in experimental animal models, GLP1 is one of the most potent insulinotropic peptides having a significant impact on beta-cell mass ( Ahren et al 2003). Just like VIP and PACAP, GLP1 belongs to the secretin family of proteins and is currently in clinical use for the treatment of patients with T2D (Dejager & Schweizer 2012). GLP1 is naturally released from the gut into circulation after a meal.…”

Section: Insulinotropic Agents For the Treatment Of Diabetesmentioning

confidence: 99%

Therapeutic potential of VIP vs PACAP in diabetes

Şanlioğlu

Karaçay²,

Balcı³

et al. 2012

Journal of Molecular Endocrinology

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Type 2 diabetes (T2D) is characterized by chronic insulin resistance and a progressive decline in beta-cell function. Although rigorous glucose control can reduce morbidity and mortality associated with diabetes, achieving optimal longterm glycemic control remains to be accomplished in many diabetic patients. As beta-cell mass and function inevitably decline in T2D, exogenous insulin administration is almost unavoidable as a final outcome despite the use of oral antihyperglycemic agents in many diabetic patients. Pancreatic islet cell death, but not the defect in new islet formation or beta-cell replication, has been blamed for the decrease in beta-cell mass observed in T2D patients. Thus, therapeutic approaches designed to protect islet cells from apoptosis could significantly improve the management of T2D, because of its potential to reverse diabetes not just ameliorate glycemia. Therefore, an ideal beta-cell-preserving agent is expected to protect beta cells from apoptosis and stimulate postprandial insulin secretion along with increasing beta-cell replication and/or islet neogenesis. One such potential agent, the islet endocrine neuropeptide vasoactive intestinal peptide (VIP) strongly stimulates postprandial insulin secretion. Because of its broad spectrum of biological functions such as acting as a potent anti-inflammatory factor through suppression of Th1 immune response, and induction of immune tolerance via regulatory T cells, VIP has emerged as a promising therapeutic agent for the treatment of many autoimmune diseases including diabetes.

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Incretin Therapies in the Management of Patients with Type 2 Diabetes Mellitus and Renal Impairment

Cited by 20 publications

References 96 publications

How are patients with type 2 diabetes and renal disease monitored and managed? Insights from the observational OREDIA study

How are patients with type 2 diabetes and renal disease monitored and managed? Insights from the observational OREDIA study

Experience with Vildagliptin in Type 2 Diabetic Patients Fasting During Ramadan in France: Insights from the VERDI Study

Therapeutic potential of VIP vs PACAP in diabetes

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