Читать книгу Clinical Dilemmas in Diabetes - Группа авторов - Страница 50

Recent knowledge regarding the heterogeneity in the extent of the β‐cell impairment and pancreatic lesions as well as the differences in circulating T‐cell and autoantibody immune signatures underscore the potential applications for incretin treatments, which improve capacity for insulin production by residual β‐cells and suppress glucagon secretion, as well as the need for therapeutics to reduce β‐cell stress co‐administered with immunomodulatory therapy to reverse autoimmunity in symptomatic T1D. Hence, therapies once considered only applicable to those with T2D may be of potential benefit for those with T1D. In this regard, ongoing T1D immunotherapy trials are investigating the potential benefits on β‐cell function in C‐peptide positive early diagnosed T1D patients.

In a post hoc analysis of pooled data from five randomized, placebo‐controlled studies, the dipeptidyl peptidase 4 (DPP‐4) inhibitor saxagliptin improved β‐cell function as assessed by HOMA2 of β‐cell function and post‐prandial C‐peptide from baseline in patients with Latent Autoimmune Diabetes in the Adult (LADA) [56]. Another small study found that sitagliptin, as an add‐on treatment to insulin, had a beneficial effect on C‐peptide decline compared with insulin alone. Moreover, a recent trial evaluated the effect of saxagliptin in combination with vitamin D3 in subjects with LADA with promising results [57]. As far as T1D is concerned, the effect of saxagliptin on immune regulation have been investigated in a phase IV trial (NCT02307695). Similarly, a phase III randomized controlled trial is evaluating the action of vildagliptin in the prevention of progressive β‐cell dysfunction in patients with newly diagnose of T1D (NCT01559025). In another ongoing study, researchers are testing the efficacy of 4 weeks rapamycin treatment and 4 weeks rapamycin treatment plus 3 months vildagliptin treatment versus placebo in increasing endogenous insulin production and correcting glycemic lability (NCT02803892). Glucagon‐like peptide (GLP‐1) analogues have been tested in large‐scale clinical trial to prove their various benefits for β‐cell and glucolipid metabolism in T2D and obesity patients. This has led to concerns regarding the potential applications in T1D patients. A small phase II randomized controlled trial (NCT02617654) is currently investigating the effect of 52 weeks of treatment with liraglutide 1.8 mg/day, compared to placebo, on stimulated C‐peptide concentrations in patients with long‐standing type 1 diabetes and residual insulin production (primary outcome: MMTT C‐peptide at 12 months).

Other studies on preservation of β‐cell function using incretin‐based therapies are currently active but not recruiting participants (NCT02443155; NCT02127047). Results from these studies are warranted to prove that incretin‐based therapy might preserve C‐peptide secretion (Table 2.3).