The incretin-based drugs glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidal peptidase 4 (DPP-4) inhibitors are a new class of drugs for the treatment of type 2 diabetes [
1]. GLP-1 is released from intestinal L cells in response to the ingestion of a meal and plays an important role in glucose homeostasis by stimulating glucose-dependent insulin secretion and inhibiting glucagon secretion [
1‐
3]. Currently, two GLP-1 analogues (exenatide and liraglutide) and four DPP-4 inhibitors (sitagliptin, vildagliptin, saxagliptin and alogliptin) are on the market, and many others are under development. The latter class of drugs works by inhibiting the DPP-4 enzyme that degrades GLP-1, thereby stabilizing the intact (active) form of GLP-1. Active GLP-1 stimulates glucose-dependent insulin biosynthesis and release, and GLP-1 also suppresses glucagon release, delays gastric emptying and increases satiety. In contrast to GLP-1 analogues, DPP-4 inhibitors have no effects on gastric emptying and body weight [
1‐
3]. Sitagliptin is the first DPP-4 inhibitor on the market. It is used as monotherapy or in combination with metformin, thiazolidinedione or sulfonylurea. It is also available in a combination product with metformin. Furthermore, its combination with insulin has recently been approved in the USA based on the large amount of clinical data [
4]. Incretin-based therapies are associated with enhanced β-cell function, making them a good treatment option early in the disease when the patients still maintain sufficient levels of β-cell function [
1‐
3]. However, it is unclear whether incretin-based drugs are still effective in patients without the capacity for endogenous insulin secretion (that is, no residual β-cell functions; for example, advanced type 2 diabetes or type 1 diabetes). Animal models have demonstrated that DPP-4 inhibitors improve glucose intolerance in early-stage diabetes, but not in the late stage of the disease [
5], suggesting that DPP-4 inhibitors are more effective in the presence of functional β-cells. However, whether this is the case in humans has not been investigated. The possibility of using GLP-1 analogues in patients with type 1 diabetes is now emerging [
6]. As in the animal model [
5], it has been proposed that the ideal candidates for this treatment strategy are individuals with type 1 diabetes who still have significant preserved β-cell activity [
6]. So far, no study has demonstrated whether DPP-4 inhibitors are also effective with those patients who absolutely lack the capacity for endogenous insulin secretion. The present report presents three cases (one with type 1 diabetes, one with type 2 diabetes and one with features of both type 1 and type 2 diabetes) where the addition of sitagliptin to the ongoing insulin therapy was considerably effective in the patients whose insulin secretory capacity (residual β-cell function) was severely diminished.