Short-Term Continuous Subcutaneous Insulin Infusion Combined with Insulin Sensitizers Rosiglitazone, Metformin, or Antioxidant α-Lipoic Acid in Patients with Newly Diagnosed Type 2 Diabetes Mellitus

Abstract

Background: Short-term continuous subcutaneous insulin infusion (CSII) in patients with newly diagnosed type 2 diabetes has been proved effective in improving metabolic control and b-cell function, thus inducing long-term drug-free remission. A randomized controlled trial was conducted to investigate whether CSII in combination with rosiglitazone, metformin, or a-lipoic acid separately brings about extra benefits. Patients and Methods: One hundred sixty patients with newly diagnosed type 2 diabetes were randomized to one of four treatment groups: CSII alone, CSII in combination with rosiglitazone or metformin for 3 months, or CSII with a-lipoic acid intravenous infusion for 2 weeks. Duration of CSII treatment was identical in the four groups. Glucose and lipid profiles, homeostasis model assessment (HOMA) indices, acute insulin response (AIR), intramyocellular lipid (IMCL) level, and malondialdehyde level were compared before and after intervention. Results: The near-normoglycemia rate at the third month in CSII alone and that in combination with rosiglitazone, metformin, or a-lipoic acid was 72.5%, 87.5%, 90%, and 75%, respectively (metformin group vs. CSII alone, P = 0.045). The metformin group achieved euglycemia in a shorter time (2.6 -1.3 vs. 3.7 -1.8 days, P = 0.020) with less daily insulin dosage and was more powerful in lowering total cholesterol, increasing AIR and HOMA b-cell function, whereas reduction of IMCL in the soleus was more obvious in the rosiglitazone group but not in the metformin group. The efficacy of combination with a-lipoic acid was similar to that of CSII alone. Conclusions: Short-term CSII in combination with rosiglitazone or metformin is superior to CSII alone, yet the efficacy of the two differs in some way, whereas that with a-lipoic acid might not have an additive effect.

Lower mean blood glucose during short‐term intensive insulin therapy is associated with long‐term glycemic remission in patients with newly diagnosed type 2 diabetes: Evidence‐based recommendations for standardization

“…Hypoglycemia is associated with glucose fluctuations, numerous adverse events and even increased mortality. In previous reports, some hypoglycemic episodes were seen during SIIT. However, to our knowledge, a detailed description of hypoglycemic events, as well as how hypoglycemia affects clinical outcomes has not been previously described, although this is important for making clinical decisions on setting glycemic targets and titrating the insulin dose.…”

Intensive insulin therapy combined with metformin is associated with reduction in both glucose variability and nocturnal hypoglycaemia in patients with type 2 diabetes

“…Previous studies confirmed that adjunct metformin with intensive therapies were associated with a significant reduction in daily insulin requirements and less increase in body weight. However, no proved reduction in HbA1c or hypoglycaemic episode was found . Therefore, when taking all these findings together, we could hardly conclude a protective effect of CSII therapy as compared with MDI therapy or benefits of metformin therapy when added to this insulin regimen regarding to reducing glucose variability and hypoglycaemic risk.…”

“…However, no proved reduction in HbA1c or hypoglycaemic episode was found. [15][16][17] Therefore, when taking all these findings together, we could hardly conclude a protective effect of CSII therapy as compared with MDI therapy or benefits of metformin therapy when added to this insulin regimen regarding to reducing glucose variability and hypoglycaemic risk.…”

Short‐term intensive insulin therapy at diagnosis in type 2 diabetes: plan for filling the gaps

“…Anecdotally, our own clinical experience with patients and their families has repeatedly shown that following STII therapy, some patients are able to sustain prolonged remissions [periods of euglycaemia] despite having discontinued drug therapy. There are also numerous formal clinical studies demonstrating that STII therapy can normalize glycaemic control, improve beta‐cell function, and/or restore first‐phase insulin secretion and decrease insulin resistance in newly diagnosed type 2 diabetes . STII therapy has also been favourably assessed in a recent meta‐analysis as well as in review articles, where it has been either the focus of the review (e.g.…”

“…To date, the clinical application of STII therapy in newly diagnosed patients has been very heterogeneous . As these reports indicate, STII therapy has been evaluated in single‐arm as well as comparative studies, conducted in hospital as well as outpatient settings, and delivered via continuous subcutaneous insulin infusion [CSII] or multiple daily injections [MDI].…”