Real-World Adequacy of Glycaemic Control in Treatment-Naïve
                    Greek Patients with Type 2 Diabetes Mellitus Initiating Treatment with Metformin
                    Monotherapy at the Maximum Tolerated Dose: The Reload Study

Vasilis Tsimihodimos; Alexandra Bargiota; Emmanouil M. Pagkalos; Christos Manes; Aggelos Papas; Eugenia Karamousouli; Bernd Voss; Moses S Elisaf

doi:10.1055/a-0824-6607

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2020; 128(04): 224-230
DOI: 10.1055/a-0824-6607

Article

Real-World Adequacy of Glycaemic Control in Treatment-Naïve Greek Patients with Type 2 Diabetes Mellitus Initiating Treatment with Metformin Monotherapy at the Maximum Tolerated Dose: The Reload Study

Vasilis Tsimihodimos

¹Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece

,

Alexandra Bargiota

²Department of Endocrinology and Metabolic Diseases, University of Thessaly School of Medicine, Larissa, Greece

,

Emmanouil M. Pagkalos

³Private Hospital Thermi Clinic, Thessaloniki, Greece

,

Christos Manes

⁴Diabetes Center, Papageorgiou General Hospital, Thessaloniki, Greece

,

Aggelos Papas

⁵Diabetes Center, Venizelio General Hospital Heraklion, Crete, Greece

,

Eugenia Karamousouli

⁶Merck Sharp & Dohme (MSD), Athens, Greece

,

Bernd Voss

⁷MSD RBSC, Lindenplatz 1, Haar Deutschland, Germany

,

Moses S Elisaf

¹Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece

› Author Affiliations

Abstract

Background Metformin, in the absence of contraindications or intolerance, is recommended as first-line treatment for patients with type 2 diabetes mellitus (T2DM). This observational, retrospective study assessed the real-world adequacy of glycaemic control in Greek patients with T2DM initiating metformin monotherapy at maximum tolerated dose.

Methods Included patients received metformin monotherapy for ≥24 months; relevant patient data were collected immediately prior to metformin initiation (baseline) and at other prespecified time points. The primary objective was to report, after 9 months of metformin treatment, the percentage of patients with baseline glycated haemoglobin (HbA_1c) levels ≥6.5% (≥48 mmol/mol) achieving HbA_1c<6.5%. Secondary objectives included the assessment of time spent with poor glycaemic control and time to treatment intensification. A sensitivity analysis assessed the percentage of patients with baseline HbA_1c≥7% (≥53 mmol/mol) achieving HbA_1c<7% (<53 mmol/mol).

Results Of the enrolled patients (N=316), 247 had baseline HbA_1c ≥6.5%; following 9 months on metformin, 90 (36.4%) patients achieved HbA_1c<6.5% (mean HbA_1c change−1.3% [−14 mmol/mol]). Median time of exposure to HbA_1c ≥6.5% was 23.4 months and time to treatment intensification was 28.0 months. The sensitivity analysis revealed that the proportion of patients achieving HbA_1c<7.0% was 50% (mean HbA_1cpy for up to 24 months. Addressing clinical inertia could improve disease outcomes and, possibly, economic burden.

Key words

clinical inertia - glycaemic control - metformin - type 2 diabetes mellitus

Full Text

References

References
1 Yokoyama H, Oishi M, Takamura H. et al. Large-scale survey of rates of achieving targets for blood glucose, blood pressure, and lipids and prevalence of complications in type 2 diabetes (JDDM 40). BMJ Open Diabetes Res Care 2016; 4: e000294
2 Inzucchi SE, Bergenstal RM, Buse JB. et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015; 38: 140-149
3 American Diabetes Association . Standards of Medical Care in Diabetes 2017, Glycemic Targets. Diabetes Care 2017; 40 (Suppl 1) S48-S56
4 Hellenic Diabetes Association. 2013 Available at http://www.diabetes. teithe.gr/UsersFiles/entypa/odigies.pdf (accessed 05 September 2018)
5 UK Prospective Diabetes Study (UKPDS) Group . Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854-865
6 Holman RR, Paul SK, Bethel MA. et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359: 1577-1589
7 Marín-Peñalver JJ, Martín-Timón I, Sevillano-Collantes C. et al. Update on the treatment of type 2 diabetes mellitus. World J Diabetes 2016; 7: 354-395
8 Khunti K, Wolden ML, Thorsted BL. et al. Clinical inertia in people with type 2 diabetes: a retrospective cohort study of more than 80,000 people. Diabetes Care 2013; 36: 3411-3417
9 Reach G, Pechtner V, Gentilella R. et al. Clinical inertia and its impact on treatment intensification in people with type 2 diabetes mellitus. Diabetes Metab 2017; 43: 501-511
10 Phillips LS, Branch WT, Cook CB. et al. Clinical inertia. Ann Intern Med 2001; 135: 825-834
11 Paul SK, Klein K, Thorsted BL. et al. Delay in treatment intensification increases the risks of cardiovascular events in patients with type 2 diabetes. Cardiovasc Diabetol 2015; 14: 100
12 Mahabaleshwarkar R, Gohs F, Mulder H. et al. Patient and provider factors affecting clinical inertia in patients with type 2 diabetes on metformin monotherapy. Clin Ther 2017; 39: 1658-1670
13 Fu AZ, Qiu Y, Davies MJ. et al. Treatment intensification in patients with type 2 diabetes who failed metformin monotherapy. Diabetes Obes Metab 2011; 13: 765-769
14 Fu AZ, Sheehan JJ. Treatment intensification for patients with type 2 diabetes and poor glycaemic control. Diabetes Obes Metab 2016; 18: 892-898
15 Giorda CB, Cercone S, Nada E. ACCADEMY Study Group. Results of the Adequacy of glycemiC Control in pAtients with type 2 Diabetes mEllitus treated with Metformin monotherapY at the maximal-tolerated dose (ACCADEMY) study. Endocrine 2016; 52: 507-515
16 Liatis S, Dafoulas GE, Kani C. et al. The prevalence and treatment patterns of diabetes in the Greek population based on real-world data from the nation-wide prescription database. Diabetes Res Clin Pract 2016; 118: 162-167
17 Kostapanos MS, Tsimihodimos V, Elisaf MS. et al. Rationale, design and baseline patient characteristics of the optimal type 2 diabetes management including benchmarking and standard treatment study in Greece. World J Diabetes 2014; 5: 76-83
18 Avramopoulos I, Moulis A, Nikas N. Glycaemic control, treatment satisfaction and quality of life in type 2 diabetes patients in Greece: The PANORAMA study Greek results. World J Diabetes 2015; 6: 208-216
19 de Pablos-Velasco P, Parhofer KG, Bradley C. et al. Current level of glycaemic control and its associated factors in patients with type 2 diabetes across Europe: data from the PANORAMA study. Clin Endocrinol (Oxf) 2014; 80: 47-56
20 Cook MN, Girman CJ, Stein PP. et al. Initial monotherapy with either metformin or sulphonylureas often fails to achieve or maintain current glycaemic goals in patients with Type 2 diabetes in UK primary care. Diabet Med 2007; 24: 350-358
21 Goldstein BJ, Feinglos MN, Lunceford JK. et al. Effect of initial combination therapy with sitagliptin, a dipeptidyl peptidase-4 inhibitor, and metformin on glycemic control in patients with type 2 diabetes. Diabetes Care 2007; 30: 1979-1987
22 Aschner P, Katzeff HL, Guo H. et al. Efficacy and safety of monotherapy of sitagliptin compared with metformin in patients with type 2 diabetes. Diabetes Obes Metab 2010; 12: 252-261
23 Sumitani S, Morita S, Utsu Y. et al. Effectiveness of metformin and lifestyle interventions as an initial treatment in Japanese patients with newly diagnosed type 2 diabetes: a prospective observational study. J Med Invest 2012; 59: 166-173
24 Umpierrez G, Tofé Povedano S, Pérez Manghi F. et al. Efficacy and safety of dulaglutide monotherapy versus metformin in type 2 diabetes in a randomized controlled trial (AWARD-3). Diabetes Care 2014; 37: 2168-2176
25 Garber AJ, Duncan TG, Goodman AM. et al. Efficacy of metformin in type II diabetes: results of a double-blind, placebo-controlled, dose response trial. Am J Med 1997; 103: 491-497
26 Hirst JA, Farmer AJ, Ali R. et al. Quantifying the effect of metformin treatment and dose on glycemic control. Diabetes Care 2012; 35: 446-454
27 Martono DP, Lub R, Lambers Heerspink HJ. et al. Predictors of response in initial users of metformin and sulphonylurea derivatives: a systematic review. Diabet Med 2015; 32: 853-864
28 UK Prospective Diabetes Study (UKPDS) Group . Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-853
29 Currie CJ, Peters JR, Tynan A. et al. Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study. Lancet 2010; 375: 481-489
30 Ahlqvist E, Storm P, Käräjämäki A. et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol 2018; 6: 361-369
31 Pantalone KM, Wells BJ, Chagin KM. et al. Intensification of diabetes therapy and time until a1c goal attainment among patients with newly diagnosed type 2 diabetes who fail metformin monotherapy within a large integrated health system. Diabetes Care 2016; 39: 1527-1534
32 Mata-Cases M, Franch-Nadal J, Real J. et al. Glycaemic control and antidiabetic treatment trends in primary care centres in patients with type 2 diabetes mellitus during 2007-2013 in Catalonia: a population-based study. BMJ Open 2016; 5 6: e012463 doi:10.1136/bmjopen-2016-012463
33 Ross SA. Breaking down patient and physician barriers to optimize glycemic control in type 2 diabetes. Am J Med 2013; 126: S38-S48
34 Svensson E, Baggesen LM, Johnsen SP. et al. Early glycemic control and magnitude of hba1c reduction predict cardiovascular events and mortality: population-based cohort study of 24,752 metformin initiators. Diabetes Care 2017; 40: 800-807