In Focus
73rd Scientific Sessions of the American Diabetes Association DCCT/EDIC: 30th anniversary New results from the Diabetes Control and Complications Trial (DCCT) trial and subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up observational study were presented in a special session. At the 30 year milestone of the DCCT/EDIC, around 1270 of the 1441 patients with type 1 diabetes initially enrolled in the DCCT trial (95% of the survivors) are still being followed in the EDIC study. In DCCT, half of the patients were randomly assigned to receive intensive insulin therapy, aimed at achieving glycemic control as close to the nondiabetic range as safely possible, and the other half to receive standard care. The large benefits recorded in patients who received intensive treatment have led to this protocol becoming the gold standard for care of patients with type 1 diabetes. Although treatment options did not differ between the groups after the completion of DCCT in 1993, differences are still reported between the two groups as a result of the treatment they were initially randomly assigned to receive. For example, a 30–46% greater risk of progression and incidence of diabetic retinopathy is seen in the standard care group. In addition, those in the intensive treatment group have a 50% reduced risk of impaired renal function. The ocular and renal differences reported between groups can be almost exclusively attributed to the patients’ glycaemic control during DCCT. A surprising finding that has only become evident in recent analyses is that some kind of cheiroarthropathy, the most common manifestation being frozen shoulder, has arisen in two-thirds of the total population. Although incidence does not seem to depend on treatment assignment during DCCT, incidence is associated with glycaemic control. The longterm outcome data will continue to
inform clinical practice and future studies. The mean age of the patient population is now in the mid-fifties, and the oldest patient is 69 years old. As this population ages, potential is unparalleled for the study of the effect of type 1 diabetes and early intensive treatment on disorders generally seen in old age, such as dementia and hearing impairment.
Psoriasis drug could induce remission in type 1 diabetes Early results of the T1DAL trial, presented by Mark Rigby (University of Indiana, Indianapolis, IN, USA), suggest that alefacept, which has been approved by the US Food and Drug Administration (FDA) for the treatment of psoriasis, can prevent autoimmune destruction of pancreatic β cells in patients with new-onset type 1 diabetes. In this double-blind, phase 2, randomised controlled trial, 49 newly diagnosed patients received either 15 mg alefacept (n=33) or placebo (n=16) once per week for two 12-week courses, with a 12-week pause in between courses. No significant differences were reported for the primary outcome which was change in C-peptide area under the curve from a 2 h mixed meal tolerance test at 52 weeks (0·015 for alefacept and –0·115 for placebo; p=0·065). However, changes were recorded for some of the secondary outcomes: the C-peptide area under the curve from a 4 h mixed meal tolerance test at 52 weeks was significantly higher in the alefacept group than in the placebo group (0·015 vs –0·155; p=0·019). Additionally, although glycaemic control at 52 weeks was similar between groups, insulin use was lower in the alefacept group than in the placebo group (0·36 U/kg vs 0·48 U/kg per day; p=0·02). In fact, insulin use did not increase significantly from baseline in the alefacept group (0·02 U/kg per day; p=0·41).
www.thelancet.com/diabetes-endocrinology Vol 1 September 2013
Dual inhibitor of SGLT1 and SGLT2 for type 2 diabetes Pablo Lapuerta and Brian Zambrowicz (Lexicon Pharmaceuticals, The Woodlands, TX, USA) discussed results of a 12-week phase 2 trial in which LX4211 was assessed as an add-on to metformin treatment in 299 patients with type 2 diabetes. LX4211 is a novel inhibitor of both SGLT1 and SGLT2 glucose transporters. Patients were randomly assigned to receive either 75 mg, 200 mg, or 400 mg LX4211 once per day, 200 mg LX4211 twice per day, or placebo. Treatment with LX4211 reduced HbA1c concentration in a dose-dependent manner. In patients with a BMI of more than 30 kg/m2 at baseline, significant reductions in bodyweight were reported in all groups receiving more than 75 mg LX4211 per day, relative to placebo. In patients with high triglyceride concentrations (200–500 mg/dl) at baseline, LX4211 treatment significantly reduced triglyceride concentrations in all but the group receiving 200 mg LX4211 per day. Treatment with 400 mg LX4211 once per day reduced systolic blood pressure significantly more in hypertensive patients than in normotensive patients (–14 mm Hg vs –1 mm Hg relative to placebo).
Published Online July 9, 2013 http://dx.doi.org/10.1016/ S2213-8587(13)70061-5 The 73rd Scientific Sessions of the American Diabetes Association were held in Chicago, IL, USA, on June 21–25, 2013.
Stepwise intensification of prandial insulin better than basal bolus? Results of the FullSTEP study—a multinational, randomised, 32-week trial comparing the efficacy and safety of a stepwise increased prandial insulin regimen with a basalbolus prandial insulin regimen— were presented by Helena Rodbard (Rockville, MD, USA). All 401 patients in the study received insulin detemir once per day before bedtime. Half of the patients then received insulin aspart before each meal throughout the trial (basal-bolus group), and the e3
In Focus
rest initially received one injection of insulin aspart before the largest meal of the day, with additional injections added if they did not meet glycaemic targets at 11 or 22 weeks (the stepwise group). In both groups, patients selfadjusted their insulin doses once per week on the basis of fasting plasma glucose concentrations. At the end of the trial, only 44·8% of patients in the stepwise group were receiving three injections of insulin aspart per day. The change in HbA1c from baseline was not significantly different between treatment groups, showing non-inferiority of the stepwise regimen. The dropout rate was lower in the stepwise group (14%) than in the basal-bolus group (26%) and the incidence rate of hypoglycaemic episodes in the stepwise group was significantly lower than in the basal-bolus group (rate ratio 0·58 [95% CI 0·45–0·75], p
73rd Scientific Sessions of the American Diabetes Association DCCT/EDIC: 30th anniversary New results from the Diabetes Control and Complications Trial (DCCT) trial and subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up observational study were presented in a special session. At the 30 year milestone of the DCCT/EDIC, around 1270 of the 1441 patients with type 1 diabetes initially enrolled in the DCCT trial (95% of the survivors) are still being followed in the EDIC study. In DCCT, half of the patients were randomly assigned to receive intensive insulin therapy, aimed at achieving glycemic control as close to the nondiabetic range as safely possible, and the other half to receive standard care. The large benefits recorded in patients who received intensive treatment have led to this protocol becoming the gold standard for care of patients with type 1 diabetes. Although treatment options did not differ between the groups after the completion of DCCT in 1993, differences are still reported between the two groups as a result of the treatment they were initially randomly assigned to receive. For example, a 30–46% greater risk of progression and incidence of diabetic retinopathy is seen in the standard care group. In addition, those in the intensive treatment group have a 50% reduced risk of impaired renal function. The ocular and renal differences reported between groups can be almost exclusively attributed to the patients’ glycaemic control during DCCT. A surprising finding that has only become evident in recent analyses is that some kind of cheiroarthropathy, the most common manifestation being frozen shoulder, has arisen in two-thirds of the total population. Although incidence does not seem to depend on treatment assignment during DCCT, incidence is associated with glycaemic control. The longterm outcome data will continue to
inform clinical practice and future studies. The mean age of the patient population is now in the mid-fifties, and the oldest patient is 69 years old. As this population ages, potential is unparalleled for the study of the effect of type 1 diabetes and early intensive treatment on disorders generally seen in old age, such as dementia and hearing impairment.
Psoriasis drug could induce remission in type 1 diabetes Early results of the T1DAL trial, presented by Mark Rigby (University of Indiana, Indianapolis, IN, USA), suggest that alefacept, which has been approved by the US Food and Drug Administration (FDA) for the treatment of psoriasis, can prevent autoimmune destruction of pancreatic β cells in patients with new-onset type 1 diabetes. In this double-blind, phase 2, randomised controlled trial, 49 newly diagnosed patients received either 15 mg alefacept (n=33) or placebo (n=16) once per week for two 12-week courses, with a 12-week pause in between courses. No significant differences were reported for the primary outcome which was change in C-peptide area under the curve from a 2 h mixed meal tolerance test at 52 weeks (0·015 for alefacept and –0·115 for placebo; p=0·065). However, changes were recorded for some of the secondary outcomes: the C-peptide area under the curve from a 4 h mixed meal tolerance test at 52 weeks was significantly higher in the alefacept group than in the placebo group (0·015 vs –0·155; p=0·019). Additionally, although glycaemic control at 52 weeks was similar between groups, insulin use was lower in the alefacept group than in the placebo group (0·36 U/kg vs 0·48 U/kg per day; p=0·02). In fact, insulin use did not increase significantly from baseline in the alefacept group (0·02 U/kg per day; p=0·41).
www.thelancet.com/diabetes-endocrinology Vol 1 September 2013
Dual inhibitor of SGLT1 and SGLT2 for type 2 diabetes Pablo Lapuerta and Brian Zambrowicz (Lexicon Pharmaceuticals, The Woodlands, TX, USA) discussed results of a 12-week phase 2 trial in which LX4211 was assessed as an add-on to metformin treatment in 299 patients with type 2 diabetes. LX4211 is a novel inhibitor of both SGLT1 and SGLT2 glucose transporters. Patients were randomly assigned to receive either 75 mg, 200 mg, or 400 mg LX4211 once per day, 200 mg LX4211 twice per day, or placebo. Treatment with LX4211 reduced HbA1c concentration in a dose-dependent manner. In patients with a BMI of more than 30 kg/m2 at baseline, significant reductions in bodyweight were reported in all groups receiving more than 75 mg LX4211 per day, relative to placebo. In patients with high triglyceride concentrations (200–500 mg/dl) at baseline, LX4211 treatment significantly reduced triglyceride concentrations in all but the group receiving 200 mg LX4211 per day. Treatment with 400 mg LX4211 once per day reduced systolic blood pressure significantly more in hypertensive patients than in normotensive patients (–14 mm Hg vs –1 mm Hg relative to placebo).
Published Online July 9, 2013 http://dx.doi.org/10.1016/ S2213-8587(13)70061-5 The 73rd Scientific Sessions of the American Diabetes Association were held in Chicago, IL, USA, on June 21–25, 2013.
Stepwise intensification of prandial insulin better than basal bolus? Results of the FullSTEP study—a multinational, randomised, 32-week trial comparing the efficacy and safety of a stepwise increased prandial insulin regimen with a basalbolus prandial insulin regimen— were presented by Helena Rodbard (Rockville, MD, USA). All 401 patients in the study received insulin detemir once per day before bedtime. Half of the patients then received insulin aspart before each meal throughout the trial (basal-bolus group), and the e3
In Focus
rest initially received one injection of insulin aspart before the largest meal of the day, with additional injections added if they did not meet glycaemic targets at 11 or 22 weeks (the stepwise group). In both groups, patients selfadjusted their insulin doses once per week on the basis of fasting plasma glucose concentrations. At the end of the trial, only 44·8% of patients in the stepwise group were receiving three injections of insulin aspart per day. The change in HbA1c from baseline was not significantly different between treatment groups, showing non-inferiority of the stepwise regimen. The dropout rate was lower in the stepwise group (14%) than in the basal-bolus group (26%) and the incidence rate of hypoglycaemic episodes in the stepwise group was significantly lower than in the basal-bolus group (rate ratio 0·58 [95% CI 0·45–0·75], p
