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Novel newer treatment of type 2 DM

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"type 2 diabetes" AND "newer therapies"

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2026 ADA Standards of Care pharmacologic approaches type 2 diabetes GLP-1 tirzepatide SGLT2

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PMID: 38639549

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https://diabetesjournals.org/care/article/49/Supplement_1/S1…

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site:fda.gov type 2 diabetes new approval 2025 2026 tirzepatide semaglutide oral orforglipron insulin icodec

Newer treatments for type 2 diabetes mellitus

Treatment is now chosen not only to lower HbA1c, but also to reduce weight, cardiovascular risk, heart failure admissions, and kidney disease progression.
Drug groupExamplesMain advantagesImportant limitations / adverse effects
GLP-1 receptor agonistsSemaglutide, dulaglutide, liraglutideStrong HbA1c reduction, substantial weight loss, low hypoglycemia risk, cardiovascular benefit in appropriate patientsNausea, vomiting, diarrhea; usually injection, except oral semaglutide; avoid with personal/family history of medullary thyroid carcinoma or MEN2
Dual GIP/GLP-1 agonistTirzepatideAmong the most potent glucose-lowering and weight-loss therapies; once-weekly injectionSimilar gastrointestinal effects; cost and availability may limit use
SGLT2 inhibitorsEmpagliflozin, dapagliflozin, canagliflozinModest HbA1c lowering, weight and BP reduction; especially useful in heart failure and chronic kidney diseaseGenital fungal infections, volume depletion, rare euglycemic ketoacidosis; withhold during prolonged fasting, severe acute illness, and around major surgery
Once-weekly basal insulinInsulin icodec-abae (Awiqli)New option for adults with T2DM who require basal insulin: one injection weekly instead of dailyHypoglycemia remains possible; needs careful titration and is not a first choice when non-insulin agents are sufficient
Oral GLP-1 drugs in development / evolving useOral semaglutide is established; orforglipron is newer but its approval status varies by indication and countryMay avoid injectionsGI adverse effects; check local approval and indication
DPP-4 inhibitors such as sitagliptin and linagliptin are oral, weight-neutral options with little hypoglycemia, but their glucose and weight effects are less than GLP-1 based therapies or SGLT2 inhibitors. They should not be combined with a GLP-1 receptor agonist.

Practical selection

  1. Obesity or need for major weight loss
    Prefer a GLP-1 receptor agonist or tirzepatide.
  2. Heart failure, especially reduced ejection fraction
    Prefer an SGLT2 inhibitor.
  3. Chronic kidney disease, especially albuminuria
    Use an SGLT2 inhibitor if kidney function permits. Add or use a GLP-1 based agent when further glucose control, weight loss, or cardiovascular benefit is needed.
  4. Established atherosclerotic cardiovascular disease such as prior MI, stroke, or peripheral arterial disease
    Choose a GLP-1 receptor agonist with proven cardiovascular benefit and/or an SGLT2 inhibitor based on the person’s heart and kidney profile.
  5. Marked hyperglycemia or symptomatic catabolism
    Insulin may be required initially. Once-weekly insulin icodec is a newer basal-insulin option in the US for adults with T2DM, but daily basal insulin remains widely used.
  6. No major cardiorenal disease and cost is a major issue
    Metformin remains commonly used, followed by individualized additions. Sulfonylureas are inexpensive but can cause hypoglycemia and weight gain.
The 2026 ADA recommendations emphasize that SGLT2 inhibitors and GLP-1 based treatments with proven heart and kidney benefits may be started in people with T2DM plus cardiovascular disease, CKD, heart failure, or obesity irrespective of current HbA1c or metformin use. See the ADA 2026 pharmacotherapy update.
A 2024 systematic review and network meta-analysis found that SGLT2 inhibitors and GLP-1 agonists reduce major cardiovascular outcomes versus usual care; SGLT2 inhibitors particularly reduce CKD progression and heart-failure hospitalization, while GLP-1 agonists reduce stroke. See the systematic review, PMID 38639549.
Recent development: In the US, the FDA approved once-weekly insulin icodec-abae (Awiqli) in March 2026 for improving glycemic control in adults with T2DM as an adjunct to diet and exercise, documented in the FDA approval letter.
Textbook classification includes incretin-based therapies, SGLT inhibitors, insulin sensitizers, and secretagogues. Katzung's Basic and Clinical Pharmacology, 16th Edition, p. 1184.
Medication choice should be individualized by an endocrinologist or treating clinician, particularly in pregnancy, advanced kidney disease, recurrent ketoacidosis, pancreatitis history, frailty, or if insulin/sulfonylureas are already being used.
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