Comment
groups, but use of SGLT2 inhibitors was associated with greater weight loss and higher risk of genital infections after 12 weeks of treatment.9,10 SGLT2 inhibitors seem to be a useful alternative to sulfonylureas because of greater and sustainable HbA1c reductions, a low risk of hypoglycaemia, increased weight loss, and a favourable effect on cardiovascular risk factors. However, sulfonylureas are cheaper, have long-term safety data, and have a positive effect on microvascular complications.1 Hence, with an increasing number of options, the choice of second-line treatment needs to be individualised according to factors including age, hypoglycaemia risk, renal function, weight, cardiovascular disease, and the use of concomitant treatments. The results from ongoing longer head-to-head trials of the sustainability of HbA1c reductions and the safety profile of SGLT2 inhibitors —specifically cardiovascular safety—will aid the choice of a second-line treatment.
programmes sponsored by Eli Lilly and Sanofi. The views expressed in this Commentary are solely mine and not necessarily those of the National Health Service, NIHR, or UK’s Department of Health.
Abd A Tahrani
8
Centre of Endocrinology Diabetes and Metabolism, 2nd Floor, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK; and Department of Diabetes and Endocrinology, Birmingham Heartlands Hospital, Birmingham, UK [email protected]
9
I am a clinician scientist funded by the UK’s National Institute for Health Research (NIHR); have research grants from Sanofi-Aventis and NovoNordisk UK Research Foundation; and have delivered continuing medical educational
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4
5
6
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Tahrani AA, Bailey CJ, Del Prato S, Barnett AH. Management of type 2 diabetes: new and future developments in treatment. Lancet 2011; 378: 182–97. Tahrani AA, Barnett AH, Bailey CJ. SGLT inhibitors in management of diabetes. Lancet Diabetes Endocrinol 2013; 1: 140–51. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012; 35: 1364–79. Vasilakou D, Karagiannis T, Athanasiadou E, et al. Sodium-Glucose Cotransporter 2 Inhibitors for Type 2 DiabetesA Systematic Review and Meta-analysis. Ann Intern Med 2013; 159: 262–74. Ridderstråle M, Andersen KR, Zeller C, Kim G, Woerle HJ, Broedl UC, on behalf of the EMPA-REG H2H-SU trial investigators. Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial. Lancet Diabetes Endocrinol 2014; published online June 16. http://dx.doi.org/10.1016/S2213-8587(14)70120-2. Bolinder J, Ljunggren O, Johansson L, et al. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab 2014; 16: 159–69. Nauck MA, Del Prato S, Meier JJ, et al. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care 2011; 34: 2015–22. Cefalu WT, Leiter LA, Yoon KH, et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 2014; 382: 941–50. Rosenstock J, Aggarwal N, Polidori D, et al. Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes. Diabetes Care 2012; 35: 1232–38. Rosenstock J, Seman LJ, Jelaska A, et al. Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia. Diabetes Obes Metab 2013; 15: 1154–60.
The artificial pancreas—the commonly accepted term for closed-loop glucose control—combines a continuous glucose monitor, insulin pump, and control algorithm into a system that automates insulin delivery. In The Lancet Diabetes & Endocrinology, Hood Thabit and colleagues’1 multicentre, randomised crossover study assesses home-based use of overnight closed-loop insulin delivery for improvement of glucose control in 25 participants with type 1 diabetes. Extending previous work by the same group,2 the artificial pancreas system in the present study was automated, rather than manual, and was used by patients at home for 4 weeks. At-home use is a particularly notable aspect because in other outpatient trials the device was used in a controlled environment,3,4 and only one trial5 reported overnight closed-loop glucose control at home. www.thelancet.com/diabetes-endocrinology Vol 2 September 2014
The primary outcome of Thabit and colleagues’ study—the proportion of time when overnight glucose was in the target range of 3·9–8·0 mmol/L between 0000 h and 0700 h—was significantly higher during the closed-loop period compared with during the control period (mean difference between groups 13·5% (95% CI 7·3–19·7; p
groups, but use of SGLT2 inhibitors was associated with greater weight loss and higher risk of genital infections after 12 weeks of treatment.9,10 SGLT2 inhibitors seem to be a useful alternative to sulfonylureas because of greater and sustainable HbA1c reductions, a low risk of hypoglycaemia, increased weight loss, and a favourable effect on cardiovascular risk factors. However, sulfonylureas are cheaper, have long-term safety data, and have a positive effect on microvascular complications.1 Hence, with an increasing number of options, the choice of second-line treatment needs to be individualised according to factors including age, hypoglycaemia risk, renal function, weight, cardiovascular disease, and the use of concomitant treatments. The results from ongoing longer head-to-head trials of the sustainability of HbA1c reductions and the safety profile of SGLT2 inhibitors —specifically cardiovascular safety—will aid the choice of a second-line treatment.
programmes sponsored by Eli Lilly and Sanofi. The views expressed in this Commentary are solely mine and not necessarily those of the National Health Service, NIHR, or UK’s Department of Health.
Abd A Tahrani
8
Centre of Endocrinology Diabetes and Metabolism, 2nd Floor, Institute of Biomedical Research, University of Birmingham, Birmingham B15 2TT, UK; and Department of Diabetes and Endocrinology, Birmingham Heartlands Hospital, Birmingham, UK [email protected]
9
I am a clinician scientist funded by the UK’s National Institute for Health Research (NIHR); have research grants from Sanofi-Aventis and NovoNordisk UK Research Foundation; and have delivered continuing medical educational
1
2 3
4
5
6
7
10
Tahrani AA, Bailey CJ, Del Prato S, Barnett AH. Management of type 2 diabetes: new and future developments in treatment. Lancet 2011; 378: 182–97. Tahrani AA, Barnett AH, Bailey CJ. SGLT inhibitors in management of diabetes. Lancet Diabetes Endocrinol 2013; 1: 140–51. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012; 35: 1364–79. Vasilakou D, Karagiannis T, Athanasiadou E, et al. Sodium-Glucose Cotransporter 2 Inhibitors for Type 2 DiabetesA Systematic Review and Meta-analysis. Ann Intern Med 2013; 159: 262–74. Ridderstråle M, Andersen KR, Zeller C, Kim G, Woerle HJ, Broedl UC, on behalf of the EMPA-REG H2H-SU trial investigators. Comparison of empagliflozin and glimepiride as add-on to metformin in patients with type 2 diabetes: a 104-week randomised, active-controlled, double-blind, phase 3 trial. Lancet Diabetes Endocrinol 2014; published online June 16. http://dx.doi.org/10.1016/S2213-8587(14)70120-2. Bolinder J, Ljunggren O, Johansson L, et al. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab 2014; 16: 159–69. Nauck MA, Del Prato S, Meier JJ, et al. Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin: a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care 2011; 34: 2015–22. Cefalu WT, Leiter LA, Yoon KH, et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 2014; 382: 941–50. Rosenstock J, Aggarwal N, Polidori D, et al. Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes. Diabetes Care 2012; 35: 1232–38. Rosenstock J, Seman LJ, Jelaska A, et al. Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia. Diabetes Obes Metab 2013; 15: 1154–60.
The artificial pancreas—the commonly accepted term for closed-loop glucose control—combines a continuous glucose monitor, insulin pump, and control algorithm into a system that automates insulin delivery. In The Lancet Diabetes & Endocrinology, Hood Thabit and colleagues’1 multicentre, randomised crossover study assesses home-based use of overnight closed-loop insulin delivery for improvement of glucose control in 25 participants with type 1 diabetes. Extending previous work by the same group,2 the artificial pancreas system in the present study was automated, rather than manual, and was used by patients at home for 4 weeks. At-home use is a particularly notable aspect because in other outpatient trials the device was used in a controlled environment,3,4 and only one trial5 reported overnight closed-loop glucose control at home. www.thelancet.com/diabetes-endocrinology Vol 2 September 2014
The primary outcome of Thabit and colleagues’ study—the proportion of time when overnight glucose was in the target range of 3·9–8·0 mmol/L between 0000 h and 0700 h—was significantly higher during the closed-loop period compared with during the control period (mean difference between groups 13·5% (95% CI 7·3–19·7; p
