Efficacy and Safety of Lacosamide in Painful Diabetic Neuropathy

OBJECTIVE: To evaluate efficacy and safety of lacosamide compared with placebo in painful diabetic polyneuropathy. RESEARCH DESIGN AND METHODS: Diabetic patients with at least moderate neuropathic pain were randomized to placebo or lacosamide 400 (in a slow or standard titration) or 600 mg/day over 6-week titration and 12-week maintenance periods. Primary efficacy criterion was intra-individual change in average daily Numeric Pain Rating Scale score from baseline to the last 4 weeks. RESULTS: For the primary end point, pain reduction was numerically but not statistically greater with lacosamide compared with placebo (400 mg/day, P = 0.12; 600 mg/day, P = 0.18). Both doses were significantly more effective compared with placebo over the titration (P = 0.03, P = 0.006), maintenance (P = 0.01, P = 0.005), and entire treatment periods (P = 0.03, P = 0.02). Safety profiles between titration schemes were similar. CONCLUSIONS: Lacosamide reduced neuropathic pain and was well tolerated in diabetic patients, but the primary efficacy criterion was not met, possibly due to an increased placebo response over the last 4 weeks.status: publishe

Once-daily basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2 diabetes on oral hypoglycaemic agents (APOLLO) : an open randomised controlled trial

Background: As type 2 diabetes mellitus progresses, oral hypoglycaemic agents often fail to maintain blood glucose control and insulin is needed. We investigated whether the addition of once-daily insulin glargine is non-inferior to three-times daily prandial insulin lispro in overall glycaemic control in adults with inadequately controlled type 2 diabetes mellitus taking oral hypoglycaemic agents. Methods: In the 44-week, parallel, open study that was undertaken in 69 study sites across Europe and Australia, 418 patients with type 2 diabetes mellitus that was inadequately controlled by oral hypoglycaemic agents were randomly assigned to either insulin glargine taken once daily at the same time every day or to insulin lispro administered three times per day. The primary objective was to compare the change in haemoglobin A1c from baseline to endpoint (week 44) between the two regimens. Randomisation was done with a central randomisation service. Analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00311818. Findings: 205 patients were randomly assigned to insulin glargine and 210 to insulin lispro. Mean haemoglobin A1c decrease in the insulin glargine group was -1·7% (from 8·7% [SD 1·0] to 7·0% [0·7]) and -1·9% in the insulin lispro group (from 8·7% [1·0] to 6·8% [0·9]), which was within the predefined limit of 0·4% for non-inferiority (difference=0·157; 95% Cl -0·008 to 0·322). 106 (57%) patients reached haemoglobin A1c of 7% or less in the glargine group and 131 (69%) in the lispro group. In the glargine group, the fall in mean fasting blood glucose (-4·3 [SD 2·3] mmol/L vs -1·8 [2·3] mmol/L; p<0·0001) and nocturnal blood glucose (-3·3 [2·8] mmol/L vs -2·6 [2·9] mmol/L; p=0·0041) was better than it was in the insulin lispro group, whereas insulin lispro better controlled postprandial blood glucose throughout the day (p<0·0001). The incidence of hypoglycaemic events was less with insulin glargine than with lispro (5·2 [95% CI 1·9-8·9] vs 24·0 [21-28] events per patient per year; p<0·0001). Respective mean weight gains were 3·01 (SD 4·33) kg and 3·54 (4·48) kg. The improvement of treatment satisfaction was greater for insulin glargine than for insulin lispro (mean difference 3·13; 95% CI 2·04-4·22). Interpretation: A therapeutic regimen involving the addition of either basal or prandial insulin analogue is equally effective in lowering haemoglobin A1c. We conclude that insulin glargine provides a simple and effective option that is more satisfactory to patients than is lispro for early initiation of insulin therapy, since it was associated with a lower risk of hypoglycaemia, fewer injections, less blood glucose self monitoring, and greater patient satisfaction than was insulin lispro. Funding: Sanofi-Aventis

Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and combined therapy in patients with micro-and macroalbuminuria and other cardiovascular risk factors: a systematic review of randomized controlled trials

Background. A recent clinical trial showed harmful renal effects with the combined use of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor blockers (ARB) in people with diabetes or vascular disease. We examined the benefits and risks of these agents in people with albuminuria and one or more cardiovascular risk factors.Methods. MEDLINE, EMBASE and Renal Health Library were searched for trials comparing ACEI, ARB or their combination with placebo or with one another in people with albuminuria and one or more cardiovascular risk factor.Results. Eighty-five trials (21 708 patients) were included. There was no significant reduction in the risk of all-cause mortality or fatal cardiac-cerebrovascular outcomes with ACEI versus placebo, ARB versus placebo, ACEI versus ARB or with combined therapy with ACEI + ARB versus monotherapy. There was a significant reduction in the risk of nonfatal cardiovascular events with ACEI versus placebo but not with ARB versus placebo, ACEI versus ARB or with combined therapy with ACEI + ARB versus monotherapy. Development of end-stage kidney disease and progression of microalbuminuria to macroalbuminuria were reduced significantly with ACEI versus placebo and ARB versus placebo but not with combined therapy with ACEI + ARB versus monotherapy.Conclusions. ACEI and ARB exert independent renal and nonfatal cardiovascular benefits while their effects on mortality and fatal cardiovascular disease are uncertain. There is a lack of evidence to support the use of combination therapy. A comparative clinical trial with ACE, ARB and its combination in people with albuminuria and a cardiovascular risk factor is warranted