Combination treatment for T2DM Date of approval: December 2016 SAGLB.DIA.16.08.0657
Abbreviations ADA: American Diabetes Association CVD: Cardiovascular disease DPP-4: Dipeptidyl Peptidase-4 EASD: European Association for the Study of Diabetes : Glucagon-like peptide 1 : Hepatic production i: Inhibitor MACE: Major adverse cardiovascular event MET: Metformin : Receptor agonist SGLT2i: Sodium- co-transporter-2 SU: Sulphonylurea T2DM: Type 2 diabetes mellitus TZD: Thiazolidinedione
Rationale and literature search One of the important themes at ADA 2016 was the use of combination treatment regimens in T2DM This interactive graphic was created to illustrate how the use of differing drug classes in combination can be effective in moderating hyperglycemia for a patient who has not yet initiated basal insulin The focus of this document is on more recent therapies, and as such SUs and TZDs have not been included Data from clinical trials were sourced via a PubMed search This document aims to provide an overview of several classes of antihyperglycemic drugs using data from large, randomised, controlled trials For detailed information please refer to individual Summary of Product Characteristics Registration trials were included if they were randomised controlled and had reported within the past 10 years Small, observational and retrospective studies were included when no data from randomised controlled trials were available for a particular combination
The ominous octet A term coined by Professor Ralph DeFronzo during the Banting Award Lecture at the 2009 ADA Scientific Sessions, the ominous octet refers to the eight biological factors implicated in hyperglycemia in T2DM patients The ominous octet insulin Antidiabetic drug classes target different aspects of the octet Therefore, combination therapy can be individualized to better serve patients needs DFronzo. Diabetes 2009;58:773 95
Current treatment recommendations There is no one size fits all method 1 Glycemic targets and treatments should be individualised based on patient needs Current treatment model If patient not at target after 3 months then add new treatment Metformin SGLT-2i SU TZD Basal insulin In recent years, this treat-to-failure model has been questioned and it has been posited that combination therapy from the outset should be considered 2,3 1. Inzucchi SE, et al. Diabetes Care 2015;38:140 9 2. Brown JB. Diabetes Care 2004;27:1535 40 3. Del Prato S, et al. Diabetes Care 2009;32 (Suppl 2):S217 22
The benefit of combination treatment Hyperglycemia is a complex condition and monotherapy is often an insufficient method of achieving adequate glycemic control 1 The availability of several different classes of antidiabetic drugs provides the opportunity for physicians to tailor therapy to the needs of the individual patient 1,2 Initiating combination therapy from the outset has the potential to address some of the clinical inertia that can result in delayed treatment intensification, and provide a potentially beneficial effect on HbA1c and weight 2 4 While combination therapy has the potential to increase the complexity of a patient s treatment regimen the availability of fixed combinations could offset this 5 7 1. Inzucchi SE, et al. Diabetes Care 2015;38:140 9; 2. Strain WD, et al. Diabetes Res Clin Pract 2014;105:302 12 3. Khunti K, et al. Diabetes Care 2013;36:3411 7; 4. Hayden J, et al. Endocrine Abstracts 2015;38:P93 5. Rosenstock J, et al. Diabetes Care 2016; Epub ahead of print; 6. Gough SC, et al. Lancet Diabetes Endocrinol 2014;2:885 93 7. Nau DP. Am J Manag Care 2012;18(suppl 3):S49 54
Combination treatment MET + MET + SGLT2i + + MET + insulin DFronzo. Diabetes 2009;58:773 95
MET + MET + SGLT2i + + MET + insulin MET DFronzo. Diabetes 2009;58:773 95
MET + MET + MET + SGLT2i + + MET + insulin MET DFronzo. Diabetes 2009;58:773 95
MET MET + MET + SGLT2i + + MET + insulin SGLT2i MET DFronzo. Diabetes 2009;58:773 95
MET + MET + SGLT2i + + MET + insulin SGLT2i DFronzo. Diabetes 2009;58:773 95
+ MET + MET + SGLT2i + + MET + insulin DFronzo. Diabetes 2009;58:773 95
SGLT2i + MET + MET + SGLT2i + + MET + insulin SGLT2i DFronzo. Diabetes 2009;58:773 95
+ MET + MET + SGLT2i + + MET + insulin MET DFronzo. Diabetes 2009;58:773 95
MET + MET + SGLT2i + + MET + insulin SGLT2i MET DFronzo. Diabetes 2009;58:773 95
MET + MET + MET + SGLT2i + + MET + insulin SGLT2i MET DFronzo. Diabetes 2009;58:773 95
Conclusions The differing classes of available antidiabetic drugs now affords physicians the opportunity to tailor and individualise care for their patients 1 Selecting drug classes with potentially beneficial qualities such as weight loss ( and SGLT2i) can provide additional benefits to patients 1,2 However, on a patient-by-patient basis, the benefits of combining treatments should also be considered in relation to the potential for increased risk of complications While current treatment guidelines recommend initiating metformin monotherapy as first-line treatment, combination therapy in patients who are uncontrolled on metformin should be considered to address clinical inertia 1,3,4 Physicians must also be aware of the potential issue of an increased pill burden for patients which can result in poor adherence to combination therapy 5 Fixed-dose combinations of oral antihyperglycemics can reduce the complexity of a treatment regimen for patients 5 1. Inzucchi SE, et al. Diabetes Care 2015;38:140 9; 2. Hayden J, et al. Endocrine Abstracts 2015;38:P93 3. Strain WD, et al. Diabetes Res Clin Pract 2014;105:302 12; 4. Khunti K, et al. Diabetes Care 2013;36:3411 7 5. Blonde L, et al. Endocr Pract 2014;1322 32;