The choice of medication for dual-combination therapy when the treatment with metformin alone is inadequate: DiaSTATUS-2 trial outcomes

Authors: Emil Martinka
Authors‘ workplace: Národný endokrinologický a diabetologický ústav, n. o., Ľubochňa
Published in: Forum Diab 2019; 8(2): 117-127


The DiaSTATUS-2 trial was a randomized, multicentric, non-interventional, cross-sectional, retrospective study in patients with type 2 diabetes mellitus to determine the status of glycemic control at the time of intensification of the previous metformin monotherapy and the most common choice of another group of antidiabetic agents for a combination at the time of intensification, in the routine clinical practice at diabetic outpatient clinics across Slovakia, with a balanced representation of individual regions. A parallel question was to find out whether these parameters differ with respect to the presence of cardiovascular disease, the HbA1c value, and the duration of type 2 diabetes mellitus. As in other countries, the study pointed to a significant clinical inertia in the process of intensification of metformin therapy. The average HbA1c value at the time of intensification was HbA1c 8.06 ± 0.98 %, while HbA1c values averaged > 7.35 % for more than a year before intensification. In selecting the second drug, sulfonyl­urea-based drugs, followed by DPP4i and insulin, were most commonly used. For CVD-free patients, who were nearly 69.1%, this choice is acceptable, especially if the preferred sulfonylurea formulation was Gliclazide MR which presents a risk of hypoglycaemia and weight gain comparable to DPP4i, and therefore is the preferential choice for sulfonylurea-based therapy in other countries and in several therapeutic recommendations. On the other hand, in patients with cardiovascular disease (CVD+), who were 30.9%, no essential difference was found compared to CVD-free patients with regard to choosing pharmacotherapy, including cardioprotective SGLT2 and GLP1Ra, although their preference is recommended. While the use of SGLT2i in a dual combination with metformin is still limi­ted by the wording of the indication limitations (ILs), also GLP1Ra are only minimally used, although IOs allow such choice. Conversely, also in the CVD+ group, sulfonylurea was still very frequently used in a dual combination, although its cardiovascular safety (with the exception of Gliclazide MR) is being discussed until now. Also in the DIASTATUS-2 study, Gliclazide MR0 which has an EBM confirmed cardiovascular safety and renal benefit, predominated among the sulfonylurea preparations. The DIASTATUS-2 study mainly pointed to the persistent clinical inertia which, similarly to patient adherence, is a significant factor affecting both medical and economic efficacy of the treatment outcomes, in this country as well as abroad. Therefore this issue should be systematically addressed.


clinical inertia – choice of treatment after metformin – type 2 diabetes

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