Addition of exenatide or sitagliptin to insulin in new onset type 1 diabetes: A randomized, open label study

Kumar, K.V.S. Hari; Shaikh, Altamash; Prusty, Pitambar

doi:10.1016/j.diabres.2013.01.020

Cited by 77 publications

(72 citation statements)

References 19 publications

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“…Even though sitagliptin is not approved for the treatment of T1DM, we recommended this drug as an off-label treatment for these patients based on a growing body of evidence demonstrating that sitagliptin and other DPP-4 inhibitors are able to decrease the daily insulin requirement and improve metabolic control in patients with T1DM without exacerbating the risk of hypoglycemia (11, 12, 13). Another case of T1DM remission for 1 year in a patient treated with sitagliptin has been previously reported in this journal (14).…”

Section: Discussionmentioning

confidence: 99%

Four-year clinical remission of type 1 diabetes mellitus in two patients treated with sitagliptin and vitamin D3

Pinheiro

Torres

2016

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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SummaryType 1 diabetes mellitus (T1DM) is a chronic disease characterized by autoimmune destruction of pancreatic beta cells and inadequate insulin production. Remission criteria in T1DM take into account serum levels of C-peptide and glycosylated hemoglobin, as well as the dose of insulin administered to the patient. However, remission of T1DM lasting longer than 1 year is rare. We describe here the cases of two young women who presented with positive glutamic acid decarboxylase (GAD) antibody and classic clinical manifestations of T1DM. Both patients had a prior history of Hashimoto’s thyroiditis. They were initially treated with a basal-bolus regimen of insulin (glargine and lispro/glulisine). Once their blood glucose levels were controlled, they were started on oral sitagliptin 100 mg and vitamin D3 5000 IU daily. After this therapy, both patients achieved clinical diabetes remission for 4 years, along with a decrease in anti-GAD antibody levels. These benefits were probably associated with immunological effects of these medications. Inhibition of dipeptidyl peptidase 4 (DPP-4) in animal models deregulates Th1 immune response, increases secretion of Th2 cytokines, activates CD4+CD25+FoxP3+ regulatory T-cells and prevents IL-17 production. Vitamin D3 also activates CD4+CD25+FoxP3+ regulatory T-cells, and these medications combined can improve the immune response in patients with new-onset T1DM and probably promote sustained clinical remission.Learning points:The use of sitagliptin and vitamin D3 in patients with new-onset type 1 diabetes mellitus (T1DM) may help decrease the daily insulin requirement by delaying beta cell loss and improving endogenous insulin production.The use of sitagliptin and vitamin D3 in new-onset T1DM could help regulate the imbalance between Th17 and Treg cells.Age 14 years or above, absence of ketoacidosis and positive C-peptide levels in patients with T1DM are good criteria to predict prolonged T1DM remission.The determination of anti-GAD antibodies and C-peptide levels could be helpful in the follow-up of patients in use of sitagliptin and vitamin D3, which could be associated with prolonged T1DM clinical remission.

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Section: Discussionmentioning

confidence: 99%

Four-year clinical remission of type 1 diabetes mellitus in two patients treated with sitagliptin and vitamin D3

Pinheiro

Torres

2016

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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“…Nevertheless, this DPP-4 inhibitor was prescribed to our patient due to a growing body of evidence that attributes immunomodulatory effects to this pharmaceutical compound. Recent studies demonstrate that the use of sitagliptin in individuals with T1D improved overall the glycemic control and reduced insulin requirements without altering the amount of endogenous insulin production (8). Although great controversy exists in available data (8, 9), it has been proven that DPP-4 (also known as adenosine deaminase complexing protein 2 or CD26) is a transmembrane glycoprotein encoded by the DPP4 gene.…”

Section: Discussionmentioning

confidence: 99%

Combined treatment with sitagliptin and vitamin D in a patient with latent autoimmune diabetes in adults

Rapti

Karras

Grammatiki

et al. 2016

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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SummaryLatent autoimmune diabetes in adults (LADA) is a relatively new type of diabetes with a clinical phenotype of type 2 diabetes (T2D) and an immunological milieu characterized by high titers of islet autoantibodies, resembling the immunological profile of type 1 diabetes (T1D). Herein, we report a case of a young male, diagnosed with LADA based on both clinical presentation and positive anti-glutamic acid decarboxylase antibodies (GAD-abs), which were normalized after combined treatment with a dipeptidyl peptidase-4 inhibitor (DPP-4) (sitagliptin) and cholecalciferol.Learning pointsAnti-glutamic acid decarboxylase antibodies (GAD-abs) titers in young patients being previously diagnosed as type 2 diabetes (T2D) may help establish the diagnosis of latent autoimmune diabetes in adults (LADA).Sitagliptin administration in patients with LADA might prolong the insulin-free period.Vitamin D administration in patients with LADA might have a protective effect on the progression of the disease.

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“…The second open‐label study with a short‐acting GLP‐1RA in type 1 diabetes included 18 newly diagnosed adult patients randomized to standard insulin regimen, insulin + exenatide or insulin + sitagliptin (a DPP‐4 inhibitor) for a period of 12 months . The dose of sitagliptin was 100 mg once daily and exenatide was titrated to 10 µg twice daily.…”

Section: Pharmacological Glp‐1ra S In Type 1 Diabetesmentioning

confidence: 99%

Short‐acting glucagon‐like peptide‐1 receptor agonists as add‐on to insulin therapy in type 1 diabetes: A review

Albèr

Brønden

Knop

2017

Diabetes Obesity Metabolism

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A large proportion of patients with type 1 diabetes do not reach their glycaemic target of glycated hemoglobin (HbA1c) <7.0% (53 mmol/mol) and, furthermore, an increasing number of patients with type 1 diabetes are overweight and obese. Treatment of type 1 diabetes is based on insulin therapy, which is associated with well-described and unfortunate adverse effects such as hypoglycaemia and increased body weight. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are the focus of increasing interest as a possible adjunctive treatment to insulin in type 1 diabetes because of their glucagonostatic and extrapancreatic effects. So far, the focus has mainly been on the long-acting GLP-1RAs, but the risk-benefit ratio emerging from studies evaluating the effect of long-acting GLP-1RAs as adjunctive therapy to insulin therapy in patients with type 1 diabetes has been disappointing. This might be attributable to a lack of glucagonostatic effect of these long-acting GLP-1RAs in type 1 diabetes, alongside development of tachyphylaxis to GLP-1-induced retardation of gastric emptying. In contrast, the shortacting GLP-1RAs seem to have a preserved and sustained effect on glucagon secretion and gastric emptying in patients with type 1 diabetes, which could translate into effective lowering of postprandial glucose excursions; however, these observations regarding short-acting GLP1RAs are all derived from small open-label trials and should thus be interpreted with caution. In the present paper we review the potential role of GLP-1RAs, in particular short-acting GLP1RAs, as add-on to insulin in the treatment of type 1 diabetes. K E Y W O R D Santidiabetic drug, GLP-1 analogue, glucagon, incretin therapy, insulin therapy, type 1 diabetes | INTRODUCTIONTreatment of type 1 diabetes is based on insulin therapy with the goal of achieving glycated haemoglobin (HbA1c) concentration <7.0% (53 mmol/mol) to prevent micro-and macrovascular complications; however, only 13% to 19% of patients with type 1 diabetes succeed in meeting this glycaemic target.1-4 Additionally, hypoglycaemic events resulting from insulin therapy remain a serious adverse effect and might lead to both physical and psychological morbidity and mortality. 5 Insulin therapy has also been reported to result in a body weight increase, and an estimated 50% of patients with type 1 diabetes in the industrialized part of the world are now overweight or obese, with reports of 25% also having metabolic syndrome.

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Addition of exenatide or sitagliptin to insulin in new onset type 1 diabetes: A randomized, open label study

Cited by 77 publications

References 19 publications

Four-year clinical remission of type 1 diabetes mellitus in two patients treated with sitagliptin and vitamin D3

Four-year clinical remission of type 1 diabetes mellitus in two patients treated with sitagliptin and vitamin D3

Combined treatment with sitagliptin and vitamin D in a patient with latent autoimmune diabetes in adults

Short‐acting glucagon‐like peptide‐1 receptor agonists as add‐on to insulin therapy in type 1 diabetes: A review

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