The updated guidelines now prioritize therapies that lower the risk of comorbid conditions—including atherosclerotic cardiovascular disease, heart failure (HF), and chronic kidney disease—regardless of glycemic status or hemoglobin A1c (HbA1c) levels (Fig. 1) [1]. Drawing on evidence from prior randomized controlled trials, the recommendations advocate for the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors across the full spectrum of HF, whether characterized by reduced or preserved ejection fraction [1]. In patients with HF with preserved ejection fraction (HFpEF) and obesity, semaglutide (2.4 mg) has demonstrated significantly greater reductions in symptoms and physical limitations, improved exercise capacity, and enhanced weight loss compared with placebo [4]. Accordingly, for adults with type 2 diabetes mellitus, obesity, and symptomatic HFpEF, the use of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) is recommended, as it benefits glycemic control and alleviates HF-related symptoms regardless of baseline HbA1c levels [1,4].

The current guidelines now offer recommendations on selecting glucose-lowering therapies based on the presence of MASLD or metabolic dysfunction-associated steatohepatitis (MASH) (Fig. 1) [1]. For adults with type 2 diabetes mellitus who have MASH or are at high risk for liver fibrosis, agents such as pioglitazone, GLP-1 RAs, or dual therapies combining glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonism are preferred because of their potential to benefit MASH [1]. Since MASH is associated with an elevated risk of cardiovascular disease—and, when accompanied by clinically significant liver fibrosis, an increased risk of liver-related complications and death [5]—these considerations are critical. The global prevalence of MASH is rising in parallel with increasing rates of obesity and type 2 diabetes mellitus. In phase 2 trials spanning 72 weeks, the GLP-1 RA semaglutide proved effective for resolving MASH (though it did not reverse fibrosis), with response rates ranging from 40% to 59% [5]

In a separate phase 2 trial involving participants with MASH and moderate to severe fibrosis, 52 weeks of tirzepatide treatment was more effective than placebo in resolving MASH without worsening fibrosis [6]. Moreover, a greater proportion of participants in the tirzepatide arms experienced an improvement of at least one fibrosis stage without any deterioration of MASH [6]. The combined action of GIP receptor agonism with GLP-1 receptor agonism not only enhances weight loss but also exerts direct beneficial effects on white adipose tissue. Specifically, activation of GIP receptors in subcutaneous white adipose tissue increases blood flow, augments postprandial triglyceride uptake, and improves insulin sensitivity—mechanisms that may reduce ectopic fat deposition in the liver [7].

Clinical practice guidelines on MASLD from the European Association for the Study of the Liver, the European Association for the Study of Diabetes, and the European Association for the Study of Obesity recommend specific pharmacological strategies for managing type 2 diabetes mellitus in patients with MASLD [8]. These guidelines highlight the use of GLP-1 RAs, tirzepatide, SGLT2 inhibitors, and metformin, although pioglitazone is notably absent from the recommendations [8]. Additional consensus and further research are needed to resolve this discrepancy and refine treatment strategies for this population [9].

The recommendations for continuous glucose monitoring (CGM) have been expanded to include not only individuals on any insulin regimen but also patients with type 2 diabetes mellitus managed with non-insulin glucose-lowering medications [2]. Both real-time CGM (rtCGM) and intermittently scanned CGM (isCGM) are now advised for diabetes management in youths and adults on insulin therapy [2]. Furthermore, the use of rtCGM or isCGM may be considered for adults with type 2 diabetes mellitus who are not using insulin to help achieve and maintain individualized glycemic targets [2]. For many nonpregnant adults utilizing CGM, a target time-in-range (TIR) exceeding 70% within the 70 to 180 mg/dL interval is appropriate [10]. To prevent hypoglycemia, it is also recommended that the time-below-range (TBR) be kept under 4% for glucose readings below 70 mg/dL and under 1% for those below 54 mg/dL [10]. Thus, the primary objective for effective and safe glycemic control is to maximize TIR while minimizing TBR. Retrospective studies have shown a strong correlation between TIR and HbA1c, with a 70% TIR roughly corresponding to an HbA1c of approximately 7% [11]. Specific TIR targets have also been suggested for pregnant individuals with type 1 diabetes mellitus, recommending a TIR greater than 70% within a range of 63 to 140 mg/dL during pregnancy [10]. Although similar sensor glucose targets are applied to pregnant individuals with type 2 diabetes mellitus and those with gestational diabetes mellitus, the precision of quantifying TIR within these ranges remains undetermined due to insufficient data [10].

Regardless of HbA1c levels, current diabetes management now prioritizes treatment strategies based on the presence of comorbidities to mitigate associated risks. The updated guidelines further incorporate recommendations for selecting glucose-lowering medications in the context of conditions such as MASLD. Moreover, advances in diabetes technology have notably broadened the clinical applications of CGM. These updates, supported by robust evidence from high-quality clinical studies, pave the way for a more personalized and effective approach to diabetes management.