Elevated hemoglobin A (HbA) values correlate with microvascular and macrovascular complications. Thus, patients with type 2 diabetes mellitus (T2DM) are at an increased risk of developing macrovascular events. Treatment of T2DM should be based on a multifactorial approach because of its evidence regarding reduction of macrovascular complications and mortality in T2DM. It is well known that intensive glucose control reduces the risk of microvascular complications in T2DM, but the effects of antidiabetic drugs on macrovascular complications and mortality in T2DM are less clear. The results of recent trials have demonstrated clear evidence that empagliflozin and liraglutide reduce cardiovascular (CV) and all-cause mortality in T2DM, an effect that is absent in other members of antidiabetic drugs. Empagliflozin is a member of a novel class of antidiabetic drugs, the sodium-glucose co-transporter 2 (SGLT2) inhibitors. Two ongoing randomized clinical trials involving other SGLT2 inhibitors, canagliflozin and dapagliflozin, will provide additional evidence of the beneficial effects of SGLT2 inhibitors in T2DM population. The aim of this paper is to systematically present the latest evidence regarding the usage of antidiabetic drugs, and the reduction of macrovascular complications and mortality. A special emphasis is put on the novel class of antidiabetic drugs, of SGLT2 inhibitors. Key messages Macrovascular complications and mortality are best clinical trial endpoints for evaluating the efficacy of antidiabetic drugs. The first antidiabetic drug that demonstrated a reduction in mortality in the treatment of type 2 diabetes mellitus (T2DM) was empagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor. SGLT2 inhibitors are novel class of antidiabetic drugs that play a promising role in the treatment of T2DM.

BACKGROUNDObesity is a global health challenge with few pharmacologic options. Whether adults with obesity can achieve weight loss with once-weekly semaglutide at a dose of 2.4 mg as an adjunct to lifestyle intervention has not been confirmed. METHODSIn this double-blind trial, we enrolled 1961 adults with a body-mass index (the weight in kilograms divided by the square of the height in meters) of 30 or greater (≥27 in persons with ≥1 weight-related coexisting condition), who did not have diabetes, and randomly assigned them, in a 2:1 ratio, to 68 weeks of treatment with once-weekly subcutaneous semaglutide (at a dose of 2.4 mg) or placebo, plus lifestyle intervention. The coprimary end points were the percentage change in body weight and weight reduction of at least 5%. The primary estimand (a precise description of the treatment effect reflecting the objective of the clinical trial) assessed effects regardless of treatment discontinuation or rescue interventions. RESULTSThe mean change in body weight from baseline to week 68 was −14.9% in the semaglutide group as compared with −2.4% with placebo, for an estimated treatment difference of −12.4 percentage points (95% confidence interval [CI], −13.4 to −11.5; P<0.001). More participants in the semaglutide group than in the placebo group achieved weight reductions of 5% or more (1047 participants [86.4%] vs. 182 [31.5%]), 10% or more (838 [69.1%] vs. 69 [12.0%]), and 15% or more (612 [50.5%] vs. 28 [4.9%]) at week 68 (P<0.001 for all three comparisons of odds). The change in body weight from baseline to week 68 was −15.3 kg in the semaglutide group as compared with −2.6 kg in the placebo group (estimated treatment difference, −12.7 kg; 95% CI, −13.7 to −11.7). Participants who received semaglutide had a greater improvement with respect to cardiometabolic risk factors and a greater increase in participant-reported physical functioning from baseline than those who received placebo. Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%]). CONCLUSIONSIn participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight. (Funded by Novo Nordisk; STEP 1 ClinicalTrials.gov number, NCT03548935).

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male patients with breast cancer. The authors presented both mortality analyses and survival analyses. Overall survival was the primary outcome and was defined as months from cancer diagnosis to death of any cause. The difference in survival between men and women was reported for 3-year, 5-year, and overall survival and stratified by disease stage.During the study period (January 2004 through December 2014), the incidence of breast cancer in women 40 years and older in the United States was greater than 200 in 100 000 women. 2 During the same period, more than 60% of women 40 years and older underwent breast cancer screening. 3 Hence, a rather large number of the included breast cancers in women would have been detected at screening.The lead time, ie, the latency between the time of diagnosis with screening and the time that the cancer would have been diagnosed in the absence of screening, causes artificially prolonged survival times, sometimes up to several years. 4 These artificially prolonged survival times apply to all screening-detected cancers, thus causing a lead-time bias when comparing men and women. Correcting for lead time would provide a more accurate indication of the size of the problem. 4,5

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Current trends in healthcare expenditures suggest an increase at alarmingly high rates. In Europe, the majority of the European Union (EU) Member States recorded a higher healthcare expenditure in 2016 compared with 2011. This trend was most pronounced in Estonia, where a 45.3% higher expenditure in 2016 was recorded, compared with 2011. 1 Considering the United States' of America (USA) total health care spending increased from an estimated $1.4 trillion [13.3% of gross domestic product (GDP)] in 1996 to an estimated $3.1 trillion (17.9% of GDP) in 2016. 2 The pharmaceutical expenditure accounts roughly for one-quarter of all healthcare expenditure, and is a significant driver of rising healthcare cost. 3 In Croatia average increase in expenditure for medicines from 2015 to 2019 was 9.8% annually. Even more worrisome is the increase of 15.5% in 2019 compared with 2018. 4 To optimise investment in medicines, hospitals design a hospital medicines policy and use tendering and negotiation processes.The European Parliament approved the new Directive on public procurement in 2014, to provide equal access with fair competition for public contracts within the EU market. 5 Currently, the lowest price procurement strategy, with generic prescribing included, is the most commonly used method by governments and hospitals in optimising investments in medicines. 6

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