The global burden of type 2 diabetes mellitus (T2DM) is rapidly increasing, with India contributing significantly to the disease prevalence and associated economic burden. Despite metformin being the first-line therapy, many patients require combination treatment due to the progressive and multifactorial nature of T2DM. Fixed-dose combinations (FDCs) of drugs with complementary mechanisms may improve glycemic control, adherence, and treatment outcomes. This study has evaluated efficacy and safety of FDC of dapagliflozin (DAPA), glimepiride (GLIM), and metformin (MET) immediate release (IR) tablet versus co-administration of GLIM and MET tablets in patients with T2DM. This phase 3, randomized, open-label study included 536 Indian patients with T2DM [glycated hemoglobin (HbA1c) ≥ 8.0
In the phase 3 MajesTEC-3 study (NCT05083169), teclistamab with daratumumab (Tec-Dara) significantly improved progression-free and overall survival (PFS/OS) versus investigator’s choice of standard-of-care daratumumab/pomalidomide/dexamethasone (DPd) or daratumumab/bortezomib/dexamethasone (DVd) in patients with relapsed/refractory multiple myeloma (RRMM) after 1–3 prior lines of therapy (pLOTs). Of the DPd/DVd patients, 85.5
Activated phosphoinositide 3-kinase delta syndrome (APDS) is an ultra-rare disease associated with immunodeficiency and immune dysregulation. Management may include sirolimus and immunoglobulin replacement therapy (IRT); neither is specifically approved for APDS in the USA. This systematic literature review evaluated the effectiveness and safety of sirolimus and IRT in patients with APDS. MEDLINE, Embase, and Cochrane Library databases were searched through July 2025, supplemented by grey literature and bibliographic searches. Eligible records reported treatment outcomes in patients with APDS receiving sirolimus and/or IRT. Quality assessment was performed; findings were narratively synthesized. Seventy-nine records (82 publications) were included: 69 case reports of 103 patients, 8 retrospective cohort studies, and 2 case series, describing 136 treatment regimens. No prospective studies were identified. Evidence was dominated by case reports (87.3
The introduction of sodium-glucose cotransporter-2 (SGLT2) inhibitors and incretin-based therapies has transformed the management of obesity, type 2 diabetes, heart failure, and chronic kidney disease by delivering substantial metabolic, cardiovascular, and renal benefits. However, their effects on skeletal muscle have become a growing area of interest. While SGLT2 inhibitors induce modest weight loss, their catabolic metabolic effects have prompted questions regarding skeletal muscle preservation, particularly in individuals with limited physiological reserve. Conversely, the profound weight loss achieved with incretin-based therapies has raised concerns about accompanying reductions in lean tissue and their potential functional consequences. In this narrative review, we critically evaluate the available evidence regarding the effects of these therapeutic classes on skeletal muscle, integrating findings from randomized controlled trials, observational studies, systematic reviews, and mechanistic investigations. We compare their distinct biological mechanisms; summarize clinical evidence on changes in muscle quantity, quality, strength, and physical performance; and discuss their implications for older adults; individuals with frailty, sarcopenia, or sarcopenic obesity; and patients with heart failure or chronic kidney disease. Overall, current evidence indicates that both SGLT2 inhibitors and incretin-based therapies preferentially reduce adipose tissue, whereas the accompanying reductions in lean tissue are generally proportional to the magnitude of weight loss. Importantly, reductions in lean tissue should not be equated with treatment-induced sarcopenia, as current evidence does not consistently demonstrate clinically meaningful impairment in muscle strength or physical performance. Nevertheless, the populations most susceptible to skeletal muscle dysfunction remain underrepresented in clinical trials. We discuss a phenotype-based approach that integrates skeletal muscle health into therapeutic decision-making and outline practical strategies—including resistance exercise, adequate protein intake, and individualized monitoring—to preserve muscle function during treatment. Future research should prioritize standardized functional outcomes and dedicated studies in vulnerable populations to enable precision cardiorenal-metabolic medicine.
As a result of a variety of pathophysiological mechanisms, type 2 diabetes displays notable clinical heterogeneity. However, large cohorts of newly diagnosed patients are still needed to validate systematic classification based on basic clinical indicators and its clinical significance. Patients with new-onset type 2 diabetes were divided into four pathophysiological subtypes based on HOMA-IR and HOMA-β. Each subtype’s clinical traits, metabolic profiles, and cross-sectional complication risk were assessed. A total of 21,340 patients who had just received a diagnosis of type 2 diabetes and were not receiving treatment were included. HOMA-IR and HOMA-β were computed. The overall medians were used as cut points to split patients into four groups: group 1, high resistance low secretion (HRLS); group 2, high resistance high secretion (HRHS); group 3, low resistance low secretion (LRLS); and group 4, low resistance high secretion (LRHS). The groups were compared in terms of prognosis, islet function, metabolic markers, and demographics. There were notable clinical and metabolic variations among the four groups. The HRLS group (n = 2743) had the highest risk of complications, the lowest disposition index, and the worst metabolic indicators. With the highest insulin levels and a moderate disposition index, the HRHS group (n = 7935) demonstrated typical metabolic syndrome. The LRLS group (n = 7927) demonstrated severe insulin secretory defects, as evidenced by their moderate disposition index, good sensitivity, and poor secretion. The LRHS group (n = 2735) had the highest disposition index and the least severe metabolic abnormalities. All intergroup comparisons had a p value < 0.001. Type 2 diabetes subtypes with different pathophysiological mechanisms and clinical prognoses can be effectively identified by simple classification based on HOMA-IR and HOMA-β, which offers a useful framework for precision medicine.
