Recent advances in the treatment of type 2 diabetes mellitus using new drug therapies

Abstract

Several recent advances provide multiple health benefits to individuals with type 2 diabetes mellitus (T2DM). Pharmacological therapy is governed by person‐centered factors, including comorbidities and treatment goals. Adults with T2DM who have an established/high risk of atherosclerotic cardiovascular disease, heart failure, and/or chronic kidney disease, require a treatment regimen that includes agents that are proven to reduce cardiorenal risk. Weight management plays a key role in reducing glucose for patients with T2DM. A glucose‐reduction treatment regimen must consider weight management. Sodium glucose co‐transporter 2 (SGLT2) inhibitors reduce the risk of heart failure, cardiovascular and renal events. Glucagon‐like peptide‐1 (GLP‐1) receptor agonists allow better control of glycemia, promote weight loss and reduce the risk of cardiovascular events. Newer Glucose‐dependent insulinotropic polypeptide (GIP) and GLP‐1 dual agonist, which activate GIP and GLP‐1 receptors improve glycemic control and promote greater weight loss than GLP‐1 receptor agonists. Several novel drugs are in the clinical development phase. This review pertains to recent advances in pharmacological management of type 2 diabetes.

1. INTRODUCTION

The American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) consensus report in 2022 recommends more comprehensive and individualized management for subjects with T2DM, taking into consideration their specific circumstances and preferences. Clinical trials of SGLT2 inhibitors (SGLT2i) and GLP‐1 receptor agonists (GLP‐1 RA) show that there is better protection of organs of the cardiorenal system, beyond glycemic control. Their role in the treatment of T2DM is important and makes significantly increases the number of treatment options for T2DM. ¹

1.1. Changes in the treatment of T2DM

Before 2018, metformin was a first‐line drug that was recommended by the position statement of the ADA and EASD for the treatment of T2DM. If the HbA1c target is not met, any other anti‐diabetic agents can be added sequentially as second‐ and third‐line drugs. However, this strategy has changed in recent years (see Figure 1).

FIGURE 1.

Changes in T2DM treatment algorithms (graph is modified from ref. ¹ and ref. ³ ). ASCVD, Atherosclerotic cardiovascular disease; CKD, chronic kidney disease; CV, cardiovascular; DPP4i, dipeptidyl peptidase‐4 inhibitor; DSMES, diabetes self‐management and education support; GLP‐1 RA, Glucagon‐like peptide‐1 receptor agonist; HF, heart failure; SGLT2i, sodium‐glucose cotransport 2 inhibitor; SDOH, social determinants of health; SU, sulphonylurea; TZD, thiazolidinedione.

1.1.1. From glucose‐centered to individual treatment

The management of T2DM has evolved from a glucose‐centered approach, which focuses solely on controlling blood glucose levels, to an individual approach that accounts for the unique characteristics and needs of each patient, ¹ , ² including specific blood glucose and weight goals, the potential effect on weight, the risk of hypoglycemia, and prevention of cardiovascular and kidney complications. The accessibility, cost, and availability of medications are also important. The current approach to T2DM management involves a holistic and patient‐centered approach that improves outcomes and quality of life for patients who have T2DM. ¹

1.1.2. From sequential to early combination

A sequential approach uses an initial single oral glucose‐lowering medication and then other medications are added over time if the treatment fails. This approach has limitations because many patients do not quickly achieve glycemic targets and the risk of complications increases over time. A more recent recommendation is to provide an early combination of two or more agents to achieve glycemic targets more quickly and reduce the risk of complications.

A trial of Vildagliptin Efficacy in combination with metfoRmIn for early treatment for type 2 diabetes (VERIFY) determined the effect of early combination treatment for patients who were newly diagnosed as having T2DM and showed there is a significantly less likelihood of initial treatment failure than for the group receiving monotherapy throughout the 5‐year study period. ⁴

1.1.3. Reduced use of metformin as a first‐line drug

Metformin is a first‐line therapy because it has a beneficial effect on A1C, weight, and cardiovascular mortality. ⁵ However, individuals with T2DM who have either established ASCVD or who are at high risk of developing ASCVD, heart failure, or chronic kidney disease are advised to also use a medication such as a SGLT2i or GLP‐1 RA, which is proven to improve cardiorenal outcomes. This recommendation does not depend on A1C levels or whether patients are using metformin: it depends on individual status. ¹

1.1.4. The importance of weight management

Obesity and excess body weight are major risk factors for the development of T2DM and weight loss has been shown to improve control of glycemia and to reduce the risk of diabetes complications. Remission from diabetes can be achieved if there is a weight loss of 15% or more. Obesity management is a mainstay in treatment for adiposity‐related T2DM. ⁶

2. NEWLY DEVELOPED DRUGS THAT PROTECT ORGANS, OTHER THAN VIA GLYCEMIC CONTROL

2.1. SGLT2 inhibitors (SGLT2i)

2.1.1. SGLT2i for glucose control and their effect on the metabolism

SGLT2i competitively binds SGLT2 proteins in the S1 segments of the renal proximal tubules. The subsequent inhibition of co‐transporters leads to decreased glucose and sodium reabsorption and increased excretion of glucose/sodium into the urine. The effect of SGLT2i is insulin‐independent and there is a lower risk of hypoglycemia. ⁷ SGLT‐2 inhibitors reduce HbA1c levels by 0.7%–1.0%, regardless of whether the medication is used alone or in a combination therapy. SGLT‐2i has been shown to promote an average weight loss of 2–3 kg over 6 months. The use of SGLT‐2i also reduces blood pressure in some studies for up to 5 mmHg in systolic and 2 mmHg in diastolic blood pressure (Figure 2). ⁸

FIGURE 2.

Summary of the metabolic effect and the landmark trials of SGLT‐2 inhibitors. BW, body weight; CV, cardiovascular; ESKD, end‐stage kidney disease; ESRD, end‐stage renal disease; HF, heart failure; MARE, major adverse renal event; 3P MACE, 3‐point major adverse cardiovascular event; SBP, systolic blood pressure.

2.1.2. SGLT2i cardiovascular outcome trials

Several large studies show that the use of SGLT2i decreases the risk of cardiovascular events. A credible mechanism has also been identified. ⁹ The EMPA‐REG OUTCOME trial showed that empagliflozin is superior to a placebo in improving glycemic control and reducing MACE, CV death, all‐cause death and HF hospitalizations. ¹⁰

The CANVAS program demonstrated that canagliflozin significantly reduces the risk of CV events and the progression of albuminuria for T2DM patients but this study documents a greater rate of amputations and bone fractures. ¹¹ The DECLARE‐TIMI 58 trial did not demonstrate that dapagliflozin decreases CV deaths or all‐cause mortality but did show a reduced rate of hospitalization for HF and a reduction in the progression of renal failure for patients without established CV disease (Figure 2). ¹²

2.1.3. SGLT2i heart failure trials

Heart failure trials, such as the DAPA‐HF trial and the EMPEROR‐Reduced trial, determine the effect of SGLT2i on patients who have a reduced ejection fraction (HFrEF), with or without pre‐existing T2DM. The DAPA‐HF trial and the EMPEROR‐Reduced trial demonstrate that there is a beneficial effect for all individuals, regardless of whether they have T2DM. ¹³ , ¹⁴ The EMPEROR‐Preserved Trial shows that empagliflozin is the first SGLT2i agent that reduces the composite risk of cardiovascular death or hospitalization due to heart failure for patients with a preserved ejection fraction (HFpEF), regardless of whether they have diabetes. ¹⁵ The DELIVER Trial demonstrates that dapagliflozin reduces the combined risk of heart failure or cardiovascular death for patients who have experienced heart failure and who have a slightly reduced or preserved ejection fraction. ¹⁶ (Figure 2).

2.1.4. SGLT2i renal outcomes trials

Several large studies have shown that the use of SGLT2i reduces the occurrence of renal events. Credible mechanisms have also been identified. ¹⁷ The CREDENCE trial was the first randomized, double‐blind, placebo‐controlled clinical trial to determine the effect of canagliflozin on renal outcomes as an endpoint for patients with T2DM. The results of the trial show that canagliflozin reduces the risk of the primary endpoint by 30%, compared to a placebo. ¹⁸

The DAPA‐CKD trial determines the effect of dapagliflozin on renal outcomes for individuals with chronic kidney disease, regardless of whether they have diabetes. The likelihood of experiencing a pre‐specified primary endpoint is significantly reduced for the dapagliflozin treatment group than for those who are treated with a placebo. ¹⁹

The EMPA‐KIDNEY trial demonstrates that empagliflozin therapy reduces the risk of the progression of kidney disease or death from cardiovascular causes more than a placebo for patients with chronic kidney disease, including non‐albuminuria. ²⁰ (Figure 2).

These results of clinical trials inform the ADA/EASD consensus statement on the management of hyperglycemia for T2DM, which recommends the use of SGLT2i as a first‐line therapy for patients who have established atherosclerotic cardiovascular disease or heart failure and who exhibit a reduced or preserved ejection fraction and have atherosclerotic cardiovascular disease or have experienced heart failure. ¹ SGLT2i treatment has some side effects, such as volume depletion, an increased risk of genital infections, and an increased risk of diabetic ketoacidosis for some individuals. In rare cases, SGLT2 inhibitors are associated with Fournier gangrene, but the overall risk is low. ⁷ , ⁸

2.2. GLP‐1 receptor agonist (GLP‐1 RA)

2.2.1. GLP‐1 RA in glucose control and its effect on the metabolism

GLP‐1 is a peptide hormone that is secreted from the intestine, which stimulates insulin secretion and inhibits glucagon secretion in a glucose‐dependent manner. Short‐acting GLP‐1 RA results in an average decrease in HbA1c of about 0.8%–1.2%, but long‐acting GLP‐1 RA results in an average reduction in HbA1c of about 1.0%–1.8%. Average weight loss with exenatide b.i.d., lixisenatide q.d., liraglutide q.d., and dulaglutide q.w. is 2–4 kg and average weight loss with oral semaglutide q.d. and subcutaneous semaglutide q.w. is 4–6 kg. ²¹ All GLP‐1 receptor agonists reduce systolic blood pressure by 2–5 mmHg but have a less consistent effect on diastolic blood pressure. GLP‐1 receptor agonists reduce body weight and slightly reduce the lipoprotein concentration (reduction in LDL cholesterol and triglycerides). ²² They also increase pulse rate by an average of 2–5 beats per min. This increase in pulse rate does not impact the cardio‐vascular benefits, even for patients who exhibit a significant increase in heart rate. ²¹ (Figure 3).

FIGURE 3.

Summary of the metabolic effect and the landmark trials of GLP‐1 receptor agonists. BW, body weight; SBP, systolic blood pressure; 3P MACE: 3‐point major adverse cardiovascular event.

2.2.2. GLP‐1 RA cardiovascular outcome trials

The initial trial of the GLP‐1 receptor agonist, lixisenatide (ELIXA trial), showed that it has no noticeable effect on MACE, all‐cause mortality, or on hospitalization due to heart failure for patients with T2DM. ²³ The EXSCEL study used exenatide once weekly and demonstrated a negative result for cardiovascular events. ²⁴ Several cardiovascular outcomes trials using different GLP‐1 receptor agonists show a significant cardiovascular benefit. The LEADER trial, using liraglutide versus placebo, demonstrated that there is a reduction in the rate of the first occurrence of death due to cardiovascular causes, nonfatal myocardial infarction and nonfatal stroke for patients who have T2DM. The rate for all‐cause mortality is lower for the liraglutide group than for the placebo group. ²⁵

The SUSTAIN‐6 trial, which used semaglutide vs a placebo, demonstrated that there is a reduction in the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke for patients with T2DM who have a high risk of cardiovascular disease. The rate of stroke is also lower for the semaglutide group than for the placebo group. ²⁶

The REWIND trial demonstrated that for patients with type 2 diabetes who have had a prior ASCVD event or who exhibit risk factors for ASCVD, the rate of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke is significantly lower for patients who receive dulaglutide than for those who receive a placebo. The rate of stroke is lower for the dulaglutide group than for the placebo group. ²⁷

The results of the PIONEER 6 trial showed that for patients with T2DM, the rate of cardiovascular death and all‐cause mortality is lower for the orally administered semaglutide group than for the placebo group. ²⁸ (Figure 3).

2.2.3. The effect of GLP‐1 RA on the renal system

Composite renal endpoints, including progression to macro‐albuminuria, which is a measure of a substantial reduction in eGFR, so patients advance to a state of terminal renal failure and require dialysis or a kidney transplant or death due to renal causes, are significantly better for patients who are treated with liraglutide, ²⁹ semaglutide, ²⁶ or dulaglutide. ³⁰

A prespecified secondary analysis of the results of the LEADER trial shows that, when added to usual care regimens, liraglutide reduces the progression of diabetic kidney disease more than a placebo. ²⁹

An analysis of the results of the REWIND trial shows that long‐term use of dulaglutide is associated with reduced composite renal outcomes for individuals with type 2 diabetes. The most significant effect is for new macroalbuminuria, which occurs in fewer individuals in the dulaglutide group than in the placebo group. ³⁰ (Figure 3).

GLP‐1 receptor agonists have been shown to have a cardiovascular benefit so the ADA/EASD consensus statement on the management of patients with T2DM recommends the use of GLP‐1 receptor agonists as a first‐line therapy for patients who have established or are at high risk of ASCVD. ¹ Common side effects include nausea, vomiting, diarrhea and, to a lesser extent, an effect on GI tract motility, which is often managed by starting treatment with a lower dose and gradually titrating up. In rare cases, GLP‐1 receptor agonists are associated with pancreatitis and thyroid cancer, but the overall risk is low. ²¹

3. GLP‐1 AND GIP DUAL AGONIST (TIRZEPATIDE)

3.1. Mechanism for the action of Tirzepatide

Tirzepatide is a multi‐functional peptide. It is manufactured by modifying the native GIP peptide sequence to allow it to bind to GIP and GLP‐1 receptors. It is a 39‐amino‐acid linear peptide that includes a C20 fatty diacid moiety. It has a mean half‐life of about 5 days (116.7 h) so once‐weekly doses are possible. ³¹ In vitro, tirzepatide has a potency and affinity for the GIP receptor that is similar to that for native GIP. It also has a slightly weaker potency and affinity for the GLP‐1 receptor than for native GLP‐1. ³²

3.2. Therapeutic effectiveness in terms of control of glycemia and reduction in body weight

The SURPASS clinical trial program verified the therapeutic effectiveness (glycemic control and body weight reduction) and safety/tolerability to the treatment for patients with T2DM. ³³ The dose escalation starts with 2.5 mg q.w. and then increases by 2.5 mg every 4 weeks until the final maintenance dose (5, 10, or 15 mg q.w.) is achieved. ³⁴ For doses of 5 to 15 mg of tirzepatide q.w., HbA1c is reduced in SURPASS 1–5 by 1.69% to 2.58%. For doses of 5 to 15 mg of tirzepatide q.w., body weight is reduced in SURPASS 1–5 by 5.4 to 11.7 kg. A plateau is not achieved and more than 1 year may be required to achieve a new steady‐state body weight after initiating tirzepatide treatment. ³⁵

3.3. Cardiorenal effectiveness and safety

The SURPASS‐1 and ‐2 studies confirm that there is a significant reduction in triglycerides (by 18.5 to 24.8%), in LDL cholesterol (by 5.2 to 12.4%), and in VLDL cholesterol (by 17.5 to 23.7%) and a significant increase in HDL cholesterol (by 3.2%–7.9%). Changes in triglycerides and VLDL cholesterol are greater those for a treatment regimen that uses semaglutide at 1.0 mg/week. All SURPASS trials show a reduction in systolic blood pressure in a dose‐dependent manner by approximately 5–6 mmHg, which is a greater reduction than for treatment with semaglutide (by 3.6 mmHg on average) for the SURPASS‐2 study. ³⁶

The SURPASS‐4 trial determined the effect of tirzepatide treatment on cardiovascular events. Subjects with known coronary, peripheral arterial, or cerebrovascular disease or who were at high risk of developing these diseases were recruited for the study. This study did demonstrate that tirzepatide produces a greater and clinically meaningful reduction in HbA1c than glargine and that it is associated with a lower incidence of hypoglycemia at week 52. Tirzepatide treatment is not associated with excess cardiovascular risk. ³⁷ A post hoc analysis of data from the SURPASS‐4 study demonstrates that individuals who are treated with tirzepatide demonstrate a significantly lower occurrence of the composite kidney endpoint than those who are treated with insulin glargine. ³⁸

A dedicated clinical trial is currently underway to determine the cardiovascular safety and cardiovascular benefits of tirzepatide (SURPASS CVOT). This study compares the effect of tirzepatide and dulaglutide and the results will be published in 2024.

3.4. Future indications beyond T2DM

A dedicated obesity study (SURMOUNT‐1) showed that weight loss is greater for individuals who do not have T2DM than for those who have T2DM. There is a reduction of 15% to 20.9% in body weight for a dose of 5 to 15 mg tirzepatide q.w. The main reported adverse effects are nausea, diarrhea, vomiting, and constipation. ³⁹ The use of Tirzepatide q.w. to treat obesity in individuals with type 2 diabetes (SURMOUNT‐2) produces a reduction of 12.8% to 14.7% in body weight for a dose of 10 to 15 mg tirzepatide q.w. ⁴⁰ These results are significantly better than those for subcutaneous semaglutide 2.4 mg q.w. ⁴¹ and liraglutide 3.0 mg q.d. (Table 1). ⁴²

TABLE 1.

Trials for nutrient‐stimulated hormones for type 2 diabetes (phase 2 trials) and obesity for individuals with type 2 diabetes (phase 3 trials).

Trial	Phase 3 SCALE diabetes	Phase 3 STEP 2	Phase 3 SURMOUNT‐2	Phase 2	Phase 2	Phase 2
Publish	JAMA 2015;314:687–99	Lancet 2021;397:971–84	Lancet 2023;402:613–626.	Lancet 2023;402:720–730.	Lancet 2023;402:529–544.	Lancet 2023;402:472–483.
Comparator	Liraglutide (3.0 mg) versus placebo	SC. Semaglutide (2.4 mg) versus placebo	Tirzepatide (15 mg) versus placebo	Cagrilintide 2.4 mg/semaglutide 2.4 cm versus Semaglutide 2.4 mg versus cagrilintide 2.4 mg	Retatrutide 12 mg versus Dulaglutide 1.5 mg versus placebo	Oral orforglipron versus Dulaglutide 1.5 mg versus placebo
Primary endpoint	3 coprimary endpoints: △BW, △BW >5%, △BW > 10%	coprimary endpoints: △BW, △BW >5%	coprimary endpoints: △BW, △BW >5%	△HbA1c	△HbA1c	△HbA1c
Body weight change (△BW)	−6.0% versus −2.0%	−9.6% versus −3.4%	−14.7% versus −3.2%	−15.6% versus −5.1% versus −8.1%	−16.94% versus −2.02% versus −3.00%	−10.1 versus −3.9 versus −2.2 kg
Duration of study	56wk	68wk	72wk	32wk	32wk	26wk
HbA1c change (△HbA1c)				−2.2% versus −1.8% versus −0.9%	−2.02% versus −1.41% versus −0.01%	−2.10% versus −1.10% versus −0.43%

4. NOVEL AGENTS THAT ARE IN DEVELOPMENT

4.1. Amylin/GLP‐1 dual receptor agonists

Amylin is a pancreatic islet cell hormone that is co‐secreted with insulin from beta cells in response to nutrient intake. It suppresses postprandial glucagon and delays gastric emptying. Cagrilintide is a long‐acting, weekly analog of amylin that is administered subcutaneously and which is used as monotherapy and in combination with the long‐acting GLP‐1 RA semaglutide. ⁴³ A 32‐week multicenter, double blind, phase 2 trial of once weekly Cargrisema, semaglutide, or cagrilintide used 92 adults with type 2 diabetes and a BMI of 27 kg/m² or greater. The respective mean change in HbA1c from baseline to week 32 for treatment with CagriSema, semaglutide, and cagrilintide is −2.2%, −1.8%, and −0.9%, respectively. The respective mean change in bodyweight from baseline to week 32 with CagriSema, semaglutide, and cagrilintide is −15.6%, −5.1%, and −8.1%%, respectively (Table 1). ⁴⁴

4.2. GIP/glucagon/GLP‐1 triple receptor agonists

Glucagon is a 29‐amino‐acid peptide that is secreted from the alpha cells of the pancreatic islets and stimulates glycogenolysis and gluconeogenesis. The physiology of Glucagon increases blood glucose, so antagonism (rather than agonism) is the target for T2D treatments. Other studies determine the effect of Glucagon on food intake, satiety and energy expenditure.

Retatrutide is a once‐weekly, triple hormone agonist of the GIP/GLP‐1/glucagon receptor ⁴³ that is administered intravenously. A phase 2 trial used participants who have type 2 diabetes. These were randomly assigned to receive once‐weekly injections of a placebo, 1·5 mg dulaglutide or retatrutide maintenance doses of 0·5 mg, 4 mg (starting dose 2 mg), 4 mg (no escalation), 8 mg (starting dose 2 mg), 8 mg (starting dose 4 mg), or 12 mg (starting dose 2 mg). At 24 weeks, the respective least‐squares mean changes from baseline in HbA1c are −0.01%, −1.41%, −0·43%, −1·39%, −1·30%, −1·99%, −1·88%, and −2·02%. Body weight decreases in a dose dependent manner at 36 weeks by 3.00%, 2.02%, 3·19%, 7·92%, 10·37%, 16·81%, 16·34%, and 16·94%. Retatrutide produces a clinically meaningful improvement in glycemic control and a robust reduction in bodyweight and has a safety profile that is similar to that for GLP‐1 receptor agonists and GIP and GLP‐1 receptor agonists (Table 1). ⁴⁵

4.3. Oral, non‐peptide glucagon‐like peptide‐1 (GLP‐1) receptor agonist

Orforglipron is a small molecule of the non‐peptide GLP1‐receptor agonist class that is used for the management of T2DM. In preclinical and early clinical studies, Orforglipron displays a favorable oral bioavailability (20%–40%) and pharmacokinetic profile (with a half‐life of 29–49 h that is dose‐dependent). Orforglipron is being developed for the treatment of type 2 diabetes and obesity. ⁴³ The results of a 26‐week, phase 2, double‐blind, randomized, multicenter study show that Orforglipron produces a mean change in HbA1c of −2·10% (−1.67% placebo adjusted), versus −1·10% for Dulaglutide. The change in mean bodyweight at week 26 is −10.1 kg, in comparison to a reduction of 2.2 kg for a placebo and of 3.9 kg for Dulaglutide. The adverse event profile is similar to that for other GLP‐1 receptor agonists that are at a similar stage of development (Table 1). ⁴⁶

4.4. Once‐weekly basal insulin analog

New antidiabetic therapies result in significant weight loss and protection of the organs but glycemic control is the main goal in the treatment of T2DM. Insulin plays an important role in controlling blood glucose that cannot be controlled using conventional antidiabetic agents for individuals with T2DM. Current basal insulin formulations are highly effective and are associated with a reduced risk of hypoglycemia, compared with previous‐generation insulins but poor adherence to daily dosing is common and this is associated with poor glycemic control. Once weekly injections of basal insulin are predicted to reduce clinical inertia, increase treatment compliance and improve patients' quality of life, provided the risk of hypoglycemia remains low.

Insulin icodec is an insulin analog that is acylated with a C20 fatty diacid side chain, which allows strong reversible binding to albumin and leads to a reduced affinity for the insulin receptor and reduced insulin receptor‐mediated clearance. A steady‐state pharmacodynamic model shows that hypoglycemic effects are evenly distributed over the 7‐day dosing period. ⁴⁷ A randomized, open‐label, treat‐to‐target phase 3a trial used 984 adults with type 2 diabetes, who were randomly assigned in a 1:1 ratio to receive once‐weekly insulin icodec or once‐daily insulin glargine U100. The mean reduction in the glycated hemoglobin level at 52 weeks is significantly greater with icodec than for treatment with glargine U100 (−1.55% vs. −1.35%) and the percentage of time in range of 70 to 180 mg per deciliter is significantly greater for treatment with icodec than for treatment with glargine U100 (71.9% vs. 66.9%). No new safety signals were identified and adverse event rates are similar for both groups. ⁴⁸

5. CONCLUSIONS

T2DM is becoming increasingly prevalent and is one of the most important risk factors for microvascular and macrovascular complications. There has been recent progress in the treatment of T2DM. Regimes differ in terms of the method of treatment, the type and effect of drugs and the degree to which organs are protected and the weight loss that is achieved. Development is ongoing and these advances in treatment may reduce complications and improve the quality of life for individuals who have T2DM.

CONFLICT OF INTEREST STATEMENT

All authors declare no conflict of interest.

Chong K, Chang JK‐J, Chuang L‐M. Recent advances in the treatment of type 2 diabetes mellitus using new drug therapies. Kaohsiung J Med Sci. 2024;40(3):212–220. 10.1002/kjm2.12800