Initial combination therapy with linagliptin plus metformin was superior to metformin monotherapy in improving glycaemic control, with a similar safety and tolerability profile, no weight gain and a low risk of hypoglycaemia.

Following a structured in-patient diabetes training programme glycaemic control in people with Type 2 diabetes mellitus on a basal-bolus regimen improved significantly only with insulin glargine suggesting that training alone may not be sufficient to further improve metabolic control in relatively well controlled patients on NPH insulin. Therefore, in addition to a structured training programme also the insulin regimen should be optimized, e.g. by introduction of an insulin analogue.

ObjectiveTo determine the efficacy and safety of linagliptin in initial combination with metformin in patients with type 2 diabetes.MethodsThis 1-year randomised, double-blind study was an extension of a 6-month randomised controlled trial, in which adults with type 2 diabetes received one of six treatment regimens (linagliptin 2.5 mg plus metformin 500 mg bid, linagliptin 2.5 mg plus metformin mg 1000 bid, metformin 1000 mg bid, metformin 500 mg bid, linagliptin 5 mg qd or placebo). In the extension, patients in the first three treatment groups continued their regimen (non-switched group, n = 333) while the metformin 500 mg bid, linagliptin 5 mg qd and placebo groups were re-randomised to one of the three continuing regimens (switched group, n = 233).ResultsAll three non-switched groups maintained reductions in glycosylated haemoglobin (HbA1c; mean ± standard deviation reductions across the 1.5-year period: linagliptin 2.5 plus metformin 1000 bid, –1.63 ± 1.05%; linagliptin 2.5 plus metformin 500 bid, –1.32 ± 1.06%; metformin 1000 bid, –1.25 ± 0.91%) while the switched groups showed additional HbA1c reductions. During the extension, there were no clinically meaningful changes in body weight in any group. Adverse event rates were similar between groups, with most events being mild or moderate, and the incidence of investigator-defined hypoglycaemia was low, with no severe events.DiscussionInitial combination of linagliptin and metformin was well tolerated over the 1-year extension period, with low risk of hypoglycaemia, and improved glycaemic control vs. metformin alone.ConclusionThe initial combination of linagliptin and metformin appears to provide a useful treatment option in patients whose blood glucose levels are increased to an extent that metformin monotherapy may not achieve treatment targets.

Background: UKPDS suggested relentless deterioration of β cell function as a part of natural course of type 2 diabetes mellitus. However, the course was apparently not universal since many patients maintained glycemic goal (HbA1c < 7.0%) at 9 years while receiving conventional life style programs consisting of diet and exercise or/and oral agents. Moreover, β cell failure occurred around the same time as the time of onset of microvascular complications. Finally, the exact mechanism of progressive β cell failure remains to be defined. It is plausible that β cell failure may be due to fibrosis of pancreatic islets secondary to microangiopathy since no organ or tissue is exempt from this complication. Objective: To assess epidemiologic correlation between presence of β cell failure and microvascular complications by determining the prevalence of β cell failure in subjects with type 2 diabetes with increasing number of known microvascular complications. Methods: 650 Subjects with ages 40 -75 years and duration of DM 4 -23 years were divided into 4 groups according to number of microvascular complications, e.g. retinopathy, nephropathy, and neuropathy. β cell failure (β − ve ) is defined as HbA1c > 7.0% with any therapy or HbA1c < 7.0% with insulin, either monotherapy or in combination with oral agents. β cell function is deemed "preserved" (β + ve) with HbA1c < 7.0% with treatment consisting of life style program or/and oral drugs. Results: Prevalence of β cell failure progressively rose with increasing number of microvascular complications from 0 to 2 with no further significant rise with 3 complications whereas subjects with preserved β cell function declined with increasing number of microvascular * The study was presented in part at International Diabetes Federation Meeting in Dubai, UAE in December 2011. # Corresponding author. U. M. Kabadi et al.22 complications (p < 0.01 for both groups). Significant relationships were also noted between the age and the duration of diabetes and prevalence of β cell failure (p < 0.01). The relative risks rose progressively for β cell failure/β cell preserved with increasing number of microvascular complications as well as the greater duration of Diabetes. However, a significantly (p < 0.01) higher relative risk for β cell failure persisted for rising number of microvascular complications even after eliminating the influence of age and duration of diabetes. Conclusion: β cell failure may be a manifestation of microvascular pancreatic isletopathy similar to other microvascular complications.