Sitagliptin as add-on therapy in insulin deficiency: biomarkers of therapeutic efficacy respond differently in type 1 and type 2 diabetes

Abstract

BackgroundSitagliptin has been proven to be effective and safe as add-on to insulin in adult patients with type 2 diabetes and absolute insulin deficiency. Recently, it has been suggested to extend the use of dipeptidyl-peptidase-4 inhibitors to type 1 diabetes. The aim of this study was to evaluate and compare the effects of a long-term, fixed-dose combination of sitagliptin and metformin as add-on to insulin on body mass index, fasting plasma glucose, fructosamine, HbA1c, lipids, and daily dose of insulin in both type 1 diabetes and insulin-treated type 2 diabetes.MethodsWe recruited 25 patients with type 1 diabetes (mean age 51 ± 10 years, mean disease duration 26 ± 13 years) and 31 insulin-treated type 2 diabetic patients (mean age 66 ± 8 years, mean disease duration 19 ± 9 years), who received sitagliptin with metformin as a fixed-dose combination (50/1000 mg once or twice daily) or sitagliptin (100 mg once daily, if intolerant to metformin) in addition to ongoing insulin therapy for 46 ± 19 weeks and 56 ± 14 weeks, respectively.ResultsAfter 21 ± 9 weeks, patients with type 1 diabetes had a significantly lower body mass index, fasting plasma glucose, fructosamine, HbA1c, and daily insulin requirement. After 49 ± 17 weeks, they maintained their weight loss and total daily insulin dose and showed a significant reduction in low-density lipoprotein cholesterol levels, whereas their HbA1c had returned to baseline values. In patients with type 2 diabetes, long-term treatment remained weight-neutral but had persistent beneficial effects on short-term, intermediate-term, and long-term biomarkers of metabolic control, as well as on low-density lipoprotein cholesterol levels and insulin requirement.ConclusionClinical outcomes differed according to type of diabetes in terms of quality and over time. In type 2 diabetes, the combination therapy significantly improved metabolic control and the lipid profile, and decreased insulin requirements, even in the absence of clinically significant weight loss. In type 1 diabetes, the combined therapy only temporarily improved metabolic control, but significantly decreased body weight, low-density lipoprotein cholesterol levels, and insulin requirements.

Sitagliptin 100 mg vs glimepiride 1–3 mg as an add-on to insulin and metformin in type 2 diabetes (SWIM)

“…Addition of sitagliptin, a DPP-4 inhibitor for treatment of type 2 diabetes mellitus (T2DM) in patients poorly controlled on insulin with or without metformin, has been shown to reduce HbA1c and delay the need for insulin therapy (5). Sitagliptin as add-on therapy in T2DM has reported to provide persistent beneficial effects on short-term, intermediate-term and long-term biomarkers of metabolic control, as well as on low-density lipoprotein cholesterol levels and insulin requirement (6). Due to multiple actions of sitagliptin such as anti-inflammatory effect and effect on monocytes and T-lymphocytes, the clinical usefulness of the addition of sitagliptin in T2DM could be beyond glycemic reduction.…”

DPP-4 Inhibitors as Treatments for Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis

“…Unfortunately, we were unable to perform a pooled analysis of the data on the fasting blood glucose or prandial blood glucose levels because the raw data or changes were not available for some studies. Although benefits, including declining fasting blood glucose levels [ 39 ], prandial blood glucose levels [ 13 , 20 , 37 ], AUCs of 24-hour blood glucose levels [ 37 ], and HbA1c levels, as well as reductions in the insulin dosages [ 37 ], have been reported by individual studies, these effects failed to be revealed in other similar studies. The discrepancy may be caused by different baseline characteristics (such as C-peptide levels) of the enrolled populations, different lengths of follow up [ 39 ], and other variables.…”

“…Although benefits, including declining fasting blood glucose levels [ 39 ], prandial blood glucose levels [ 13 , 20 , 37 ], AUCs of 24-hour blood glucose levels [ 37 ], and HbA1c levels, as well as reductions in the insulin dosages [ 37 ], have been reported by individual studies, these effects failed to be revealed in other similar studies. The discrepancy may be caused by different baseline characteristics (such as C-peptide levels) of the enrolled populations, different lengths of follow up [ 39 ], and other variables. DPP-4 inhibitors significantly increased the GLP-1 and GIP levels [ 13 , 14 , 40 ], reduced the glucagon levels during hyperglycemia, and sustained glucagon counterregulation during hypoglycemia in patients with T1DM [ 13 , 14 ].…”

The effect of combination therapy of insulin glargine, metformin, and sitagliptin on insulin secretion, insulin resistance, and metabolic parameters in obese subjects with type 2 diabetes

“…It improves quality of life [21]. The question of biomarkers that could adequately specify the positive effects of incretin therapy in obese subjects with diabetes remains open [22,23]. HOMA indices, used in our study, are not standardized.…”