Diabetes Metab J.  2023 Mar;47(2):185-197. 10.4093/dmj.2022.0325.

Intensified Multifactorial Intervention in Patients with Type 2 Diabetes Mellitus

Affiliations
  • 1Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  • 2Diabetes Research Center, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
  • 3Department of Molecular Diabetology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan

Abstract

In the management of diabetes mellitus, one of the most important goals is to prevent its micro- and macrovascular complications, and to that end, multifactorial intervention is widely recommended. Intensified multifactorial intervention with pharmacotherapy for associated risk factors, alongside lifestyle modification, was first shown to be efficacious in patients with microalbuminuria (Steno-2 study), then in those with less advanced microvascular complications (the Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care [ADDITION]-Europe and the Japan Diabetes Optimal Treatment study for 3 major risk factors of cardiovascular diseases [J-DOIT3]), and in those with advanced microvascular complications (the Nephropathy In Diabetes-Type 2 [NID-2] study and Diabetic Nephropathy Remission and Regression Team Trial in Japan [DNETT-Japan]). Thus far, multifactorial intervention led to a reduction in cardiovascular and renal events, albeit not necessarily significant. It should be noted that not only baseline characteristics but also the control status of the risk factors and event rates during intervention among the patients widely varied from one trial to the next. Further evidence is needed for the efficacy of multifactorial intervention in a longer duration and in younger or elderly patients. Moreover, now that new classes of antidiabetic drugs are available, it should be addressed whether strict and safe glycemic control, alongside control of other risk factors, could lead to further risk reductions in micro- and macrovascular complications, thereby decreasing all-cause mortality in patients with type 2 diabetes mellitus.

Keyword

Blood pressure; Diabetes complications; Diabetes mellitus, type 2; Glycemic control; Hypoglycemia; Lipids; Mortality; Vascular diseases

Figure

  • Fig. 1. Overview of clinical trials examining effects of multifactorial intervention on cardiovascular (CV) and renal events in patients with type 2 diabetes mellitus. Start year, the country in which the trial was undertaken, the number of patients with baseline characteristics available, eligibility, and the outcome with the risk reduction during intervention of the Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care (ADDITION)-Europe [15], the Japan Diabetes Optimal Treatment study for 3 major risk factors of cardiovascular diseases (J-DOIT3) [16], the Steno-2 study [11,12], the Nephropathy In Diabetes-Type 2 (NID-2) study [17], and the Diabetic Nephropathy Remission and Regression Team Trial in Japan (DNETT-Japan) [18]. sCr, serum creatinine. aStatistically significant, bMarginally significant, cAfter adjustment for baseline characteristics, dAdditional secondary outcome.

  • Fig. 2. Cause-specific deaths in clinical trials to examine effects of intensified multifactorial treatment in patients with type 2 diabetes mellitus. Cardiovascular (CV) and non-CV deaths (% of total patients) (upper panel), and deaths due to malignant neoplasm and CV disease (% of total deaths) (lower panel), in the Steno-2 study [19], the Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen Detected Diabetes in Primary Care (ADDITION)-Europe [33], and the Japan Diabetes Optimal Treatment study for 3 major risk factors of cardiovascular diseases (J-DOIT3) [16]. Deaths due to malignant neoplasm were not available in the Steno-2 study. CV deaths in the J-DOIT3 consist of those due to myocardial infarction, stroke, heart failure, or sudden death.


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