β-Cell Function Preservation After 3.5 Years of Intensive Diabetes Therapy

Abstract

OBJECTIVETo assess β-cell function preservation after 3.5 years of intensive therapy with insulin plus metformin (INS group) versus triple oral therapy (TOT group) with metformin, glyburide, and pioglitazone.RESEARCH DESIGN AND METHODSThis was a randomized trial of 58 patients with treatment-naïve newly diagnosed type 2 diabetes. All patients were treated with insulin and metformin for a 3-month lead-in period followed by random assignment to the INS or TOT group. β-Cell function was assessed using a mixed-meal challenge test at randomization and 6, 12, 18, 30, and 42 months. Analyses were intention to treat and performed with repeated-measures models.RESULTSCompletion rates at 3.5 years were 83% in the insulin group and 72% in the TOT group, with good compliance in both groups (87 ± 20% in the INS group vs. 90 ± 15% in the TOT group). β-Cell function was preserved at 3.5 years after diagnosis, with no significant change from baseline or difference between the two groups as measured by area under the curve (AUC) of C-peptide (P = 0.14) or the ratio of C-peptide to glucose AUC (P = 0.7). Excellent glycemic control was maintained in both groups (end-of-study HbA1c 6.35 ± 0.84% in the INS group vs. 6.59 ± 1.94% in the TOT group). Weight increased in both groups over time (from 102.2 ± 24.9 kg to 106.2 ± 31.7 kg in the INS group and from 100.9 ± 23.0 kg to 110.5 ± 31.8 kg in the TOT group), with no significant difference between groups (P = 0.35). Hypoglycemic events decreased significantly over time (P = 0.01) but did not differ between groups (P = 0.83).CONCLUSIONSβ-Cell function can be preserved for at least 3.5 years with early and intensive therapy for type 2 diabetes with either insulin plus metformin or triple oral therapy after an initial 3-month insulin-based treatment period.

Assessment of beta cell function in subjects with newly diagnosed type 2 diabetes

“…Other reports with different study designs and therapeutical algorithms (e.g. longer duration of insulin therapy, use of premix or basal insulin regimens) have basically indicated the same point: insulin therapy has a beneficial effect on preservation of beta cell secretory function, even in the long term (26)(27)(28)(29). Similar to our findings, a recent paper showed that chronic treatment with longacting basal insulin improved both first-and second-phase insulin secretion (evaluated by intravenous glucose tolerance test) in hyperglycemic patients with type 2 diabetes (30).…”

Liraglutide and the Preservation of Pancreatic β-Cell Function in Early Type 2 Diabetes: The LIBRA Trial

“…Harrison et al (11) found that after an initial 3-month therapy with biphasic insulin and metformin, treatment of 58 newly diagnosed patients on either continued insulin/metformin or triple oral therapy (metformin/glyburide/pioglitazone) had stabilized measures of insulin secretion such that they neither differed from baseline nor differed between treatment arms. In patients with established T2DM, we previously showed that the improved b-cell function achieved with 4-8 weeks of prerandomization IIT was completely lost during the 48 weeks of subsequent treatment with either metformin/ sitagliptin combination therapy or metformin alone (10).…”

“…Moreover, the glucose-lowering activity of an antidiabetic medication can further confound such evaluation in patients with T2DM in whom improved b-cell function may be due to the elimination of glucotoxicity rather than to actual b-cell preservation (9). In this context, short-term treatment with insulin therapy has been proposed as a strategy for eliminating glucotoxicity before randomization, thereby creating a level playing field upon which to objectively evaluate the potential b-cell protective capacity of antidiabetic medications (9)(10)(11).…”

The Role of Diabetes Care and Its Contributions to the Field of Diabetes: A Profile in Progress

“…In 2013, an expert point-counterpoint discussion presented arguments for and against the use of incretin-based therapies, given conflicting safety data available at the time (72,73). The impact of intensive insulin treatment on the preservation of b-cell function was highlighted in studies reported in 2012 in patients with newly diagnosed type 2 diabetes (74) and in 2013 in patients with newonset type 1 diabetes (75). Recent review articles have included a summary of data on natriuretic peptides (76), a history of hyperosmolar hyperglycemic state (77), and an update on the effects of DPP-4 inhibition on microvascular complications (78).…”