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Acarbose vs metformin for new-onset type 2 diabetes
Correspondence
Acarbose vs metformin for new-onset type 2 diabetes
For the Associazione Medici Diabetologi algorithms see http://www.aemmedi.it/ algoritmi_en_2013/algoritmi. html
104
Wenying Yang and colleagues (October 18)1 report the findings of a randomised controlled trial comparing acarbose with metformin as initial therapy for Chinese patients with newly diagnosed type 2 diabetes, showing similar tolerability and efficacy. In addition to being the first head-to-head comparison of metformin and acarbose as first-line therapy for type 2 diabetes after failure of therapeutic lifestyle modification, this intervention study is interesting as it is relevant to individualisation of pharmacological antidiabetic treatment in Asian adults with type 2 diabetes. Interest in personalised diabetes treatment is increasing. Personalised therapy involves an approach to clinical decisions that is applied to each individual patient and has, as a prerequisite, an accurate characterisation of that patient (phenotyping). Personalised therapy involves applying knowledge, scientific evidence, and common sense, and taking the realities of each individual patient’s circumstances into account. The final aim is to optimise treatment responses, whilst similtaneously improving tolerability and compliance. To apply this in practice, physicians feel more comfortable having pragmatic aids such as predefined algorithms.2 Since 2010, the Italian Association of Diabetologists (Associazione Medici Diabetologi) has recognised the need to develop personalised treatment plans for patients with type 2 diabetes, taking into account the patient’s individual pattern of hyperglycaemia (phenotype), with the safest possible glycaemic control as a goal. Accordingly, tailored therapeutic algorithms have been developed for some of the most common type 2 diabetes phenotypes.3 These algorithms are available online in English, as a browser-operated
interactive instrument.4 On the basis of a patient’s clinical features, the user can access a step-by-step suggested additive therapeutic approach. In five of six Associazione Medici Diabetologi algorithms, alfa-glucosidase inhibitors are already considered as a first pharmacological option for patients who are intolerant or have contraindications to metformin and who have predominantly postprandial hyperglycaemia. The study by Yang and colleagues1 shows that eastern Asian patients with newly diagnosed type 2 diabetes, a low BMI, a high dietary carbohydrate intake, and exaggerated postprandial glucose excursion can appropriately be treated with an alfa-glucosidase inhibitor as an alternative to metformin, at least in the short term, although cardiovascular effects of acarbose have yet to be investigated fully.5 This study, in our opinion, represents a creditable contribution and a step forward towards the development of population-specific and pathophysiology-based treatment algorithms for type 2 diabetes. We declare that we have no conflicts of interest.
*Marco Gallo, Riccardo Candido, Alberto De Micheli, Katherine Esposito, Sandro Gentile, Antonio Ceriello, on behalf of Associazione Medici Diabetologi [email protected] Oncological Endocrinology, AO Città della Salute e della Scienza-Molinette, Via Genova, 3, I-10137 Turin, Italy (MG); Diabetes Center, A.S.S. 1 Triestina, Trieste, Italy (RC); Ligurian Health Agency, Genoa, Italy (ADM); Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy (KE, SG); and Insititut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain (AC) 1
2
Yang W, Liu J, Shan Z, et al. Acarbose compared with metformin as initial therapy in patients with newly diagnosed type 2 diabetes: an open-label, non-inferiority randomised trial. Lancet Diabetes Endocrinol 2013; published online Oct 18. DOI:10.1016/S22138587(13)70021-4. Stone TT, Kivlahan CH, Cox KR. Evaluation of physician preferences for guideline implementation. Am J Med Qual 1999; 14: 170–77.
3
4
5
Ceriello A, Gallo M, Armentano V, et al. Personalizing treatment in type 2 diabetes: a self-monitoring of blood glucose inclusive innovative approach. Diabetes Technol Ther 2012; 14: 373–78. Italian Association of Diabetologists (AMD). Personalisation of therapy in type 2 diabetes. http://www.aemmedi.it/algoritmi_en_2013/ (accessed Nov 26, 2013). Ma RCW. Acarbose: an alternative to metformin for first-line treatment in type 2 diabetes? Lancet Diabetes Endocrinol 2013; published online Oct 18. DOI:10.1016/S22138587(13)70107-4.
Wenying Yang and colleagues1 have reported that acarbose is similar to metformin in efficacy and a viable choice for initial therapy in Chinese patients with newly diagnosed type 2 diabetes. However, this study might have several major limitations in terms of the study design and interpretation of results. First, the study concluded non-inferiority if the upper limit of the 95% confidence interval for the treatment difference was <0·3% in HbA1c concentrations from baseline to week 48. However, add-on therapy with insulin secretagogues was initiated at week 24 in patients whose HbA1c concentrations were higher than 7%. Because the HbA1c concentrations at week 48 could be greatly affected by the other treatments except acarbose and metformin, the validity of the non-inferiority margin might not be sufficiently shown. Because this aspect was crucial to compare the efficacy of acarbose with that of metformin, the study design should have been more cautiously considered. Second, the baseline HbA1c concentrations could be misunderstood. Because there was a 4-week run-in phase of lifestyle modification before the start of initial therapy, the HbA1c concentrations in patients with newly diagnosed type 2 diabetes might have continued to be reduced for a further 1 or 2 months after study initiation, and some patients with newly diagnosed type 2 diabetes and mean HbA1c concentrations of 7·5% could have readily achieved the target HbA1c
www.thelancet.com/diabetes-endocrinology Vol 2 February 2014
Acarbose vs metformin for new-onset type 2 diabetes
For the Associazione Medici Diabetologi algorithms see http://www.aemmedi.it/ algoritmi_en_2013/algoritmi. html
104
Wenying Yang and colleagues (October 18)1 report the findings of a randomised controlled trial comparing acarbose with metformin as initial therapy for Chinese patients with newly diagnosed type 2 diabetes, showing similar tolerability and efficacy. In addition to being the first head-to-head comparison of metformin and acarbose as first-line therapy for type 2 diabetes after failure of therapeutic lifestyle modification, this intervention study is interesting as it is relevant to individualisation of pharmacological antidiabetic treatment in Asian adults with type 2 diabetes. Interest in personalised diabetes treatment is increasing. Personalised therapy involves an approach to clinical decisions that is applied to each individual patient and has, as a prerequisite, an accurate characterisation of that patient (phenotyping). Personalised therapy involves applying knowledge, scientific evidence, and common sense, and taking the realities of each individual patient’s circumstances into account. The final aim is to optimise treatment responses, whilst similtaneously improving tolerability and compliance. To apply this in practice, physicians feel more comfortable having pragmatic aids such as predefined algorithms.2 Since 2010, the Italian Association of Diabetologists (Associazione Medici Diabetologi) has recognised the need to develop personalised treatment plans for patients with type 2 diabetes, taking into account the patient’s individual pattern of hyperglycaemia (phenotype), with the safest possible glycaemic control as a goal. Accordingly, tailored therapeutic algorithms have been developed for some of the most common type 2 diabetes phenotypes.3 These algorithms are available online in English, as a browser-operated
interactive instrument.4 On the basis of a patient’s clinical features, the user can access a step-by-step suggested additive therapeutic approach. In five of six Associazione Medici Diabetologi algorithms, alfa-glucosidase inhibitors are already considered as a first pharmacological option for patients who are intolerant or have contraindications to metformin and who have predominantly postprandial hyperglycaemia. The study by Yang and colleagues1 shows that eastern Asian patients with newly diagnosed type 2 diabetes, a low BMI, a high dietary carbohydrate intake, and exaggerated postprandial glucose excursion can appropriately be treated with an alfa-glucosidase inhibitor as an alternative to metformin, at least in the short term, although cardiovascular effects of acarbose have yet to be investigated fully.5 This study, in our opinion, represents a creditable contribution and a step forward towards the development of population-specific and pathophysiology-based treatment algorithms for type 2 diabetes. We declare that we have no conflicts of interest.
*Marco Gallo, Riccardo Candido, Alberto De Micheli, Katherine Esposito, Sandro Gentile, Antonio Ceriello, on behalf of Associazione Medici Diabetologi [email protected] Oncological Endocrinology, AO Città della Salute e della Scienza-Molinette, Via Genova, 3, I-10137 Turin, Italy (MG); Diabetes Center, A.S.S. 1 Triestina, Trieste, Italy (RC); Ligurian Health Agency, Genoa, Italy (ADM); Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy (KE, SG); and Insititut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) and Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain (AC) 1
2
Yang W, Liu J, Shan Z, et al. Acarbose compared with metformin as initial therapy in patients with newly diagnosed type 2 diabetes: an open-label, non-inferiority randomised trial. Lancet Diabetes Endocrinol 2013; published online Oct 18. DOI:10.1016/S22138587(13)70021-4. Stone TT, Kivlahan CH, Cox KR. Evaluation of physician preferences for guideline implementation. Am J Med Qual 1999; 14: 170–77.
3
4
5
Ceriello A, Gallo M, Armentano V, et al. Personalizing treatment in type 2 diabetes: a self-monitoring of blood glucose inclusive innovative approach. Diabetes Technol Ther 2012; 14: 373–78. Italian Association of Diabetologists (AMD). Personalisation of therapy in type 2 diabetes. http://www.aemmedi.it/algoritmi_en_2013/ (accessed Nov 26, 2013). Ma RCW. Acarbose: an alternative to metformin for first-line treatment in type 2 diabetes? Lancet Diabetes Endocrinol 2013; published online Oct 18. DOI:10.1016/S22138587(13)70107-4.
Wenying Yang and colleagues1 have reported that acarbose is similar to metformin in efficacy and a viable choice for initial therapy in Chinese patients with newly diagnosed type 2 diabetes. However, this study might have several major limitations in terms of the study design and interpretation of results. First, the study concluded non-inferiority if the upper limit of the 95% confidence interval for the treatment difference was <0·3% in HbA1c concentrations from baseline to week 48. However, add-on therapy with insulin secretagogues was initiated at week 24 in patients whose HbA1c concentrations were higher than 7%. Because the HbA1c concentrations at week 48 could be greatly affected by the other treatments except acarbose and metformin, the validity of the non-inferiority margin might not be sufficiently shown. Because this aspect was crucial to compare the efficacy of acarbose with that of metformin, the study design should have been more cautiously considered. Second, the baseline HbA1c concentrations could be misunderstood. Because there was a 4-week run-in phase of lifestyle modification before the start of initial therapy, the HbA1c concentrations in patients with newly diagnosed type 2 diabetes might have continued to be reduced for a further 1 or 2 months after study initiation, and some patients with newly diagnosed type 2 diabetes and mean HbA1c concentrations of 7·5% could have readily achieved the target HbA1c
www.thelancet.com/diabetes-endocrinology Vol 2 February 2014