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Oscar Antidiabetic Agents - Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors & SGLT2 Antidiabetic Combinations (PG154) Form


SGLT2 Inhibitors & Antidiabetic Combinations for Type 2 Diabetes Mellitus

Notes: If all medical necessity criteria are met, the requested drug will be approved for 12 months.

Indications

(63257) Is the medication age-appropriate for the patient as per the FDA-approved indications? 
(63258) Does the patient have a diagnosis of type 2 diabetes mellitus confirmed by a fasting glucose level greater than 126 mg/dL, a 2-hour glucose tolerance test result greater than 200 mg/dL, hemoglobin A1c ≥6.5%, or symptoms of hyperglycemia plus a random plasma glucose ≥200 mg/dL? 
(63259) Has the patient tried and failed metformin at a minimum dose of 1500 milligrams daily for 90 days, or requires combination therapy with an A1c of 7.5 percent or greater? 
(63260) Does the patient have established cardiovascular disease and is requesting Farxiga, Inpefa, Invokana, or Jardiance? 
(63261) Does the patient have diabetic nephropathy with albuminuria greater than 300 mg per day and is requesting Invokana? 

YesNoN/A
YesNoN/A
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Sodium-glucose cotransporter-2 (SGLT2) inhibitors and their combination products

Sodium-glucose cotransporter-2 (SGLT2) inhibitors and their combination products represent an essential category of antidiabetic agents that reduce high blood sugar levels by decreasing renal glucose reabsorption and increasing urinary glucose excretion. They are employed to manage diabetes, a chronic medical condition characterized by high blood sugar levels resulting from inadequate insulin production by the pancreas, or the body's ineffective response to insulin.

SGLT2 inhibitors, such as Canagliflozin, Dapagliflozin, and Empagliflozin, when added to standard treatment, have been shown to reduce major adverse cardiovascular events (MACE) and hospitalization for heart failure, as well as slow the progression of chronic kidney disease (CKD) in clinical trials. However, not all SGLT2 inhibitors have demonstrated this benefit. For instance, in a double-blind trial involving patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD), Ertugliflozin did not reduce the risk of MACE.

Combination products of SGLT2 inhibitors with other antidiabetic agents offer an alternative treatment strategy, optimizing glycemic control while potentially reducing adverse events.

Diabetes management often necessitates a combination of diet, exercise, and weight loss. Although Metformin is typically the initial treatment choice, certain patients may require the addition or substitution of an SGLT2 inhibitor or an incretin mimetic such as a glucagon-like peptide-1 (GLP-1) receptor agonist. The choice of a second antihyperglycemic drug generally depends on the presence of comorbid conditions such as ASCVD, heart failure (HF), CKD, and obesity.

NOTE:
  1. The Plan requires that members either be unable to use, or have tried and failed preferred medication(s) first. Requests for non-formulary medications are subject to Medical Necessity Criteria for Non-Formulary Products (PG069).
  2. Coverage for prescription medications intended for obesity treatment, weight loss, weight reduction, or dietary control is determined by each member's specific benefit policy. Please refer to the member’s benefit plan document for information on benefit eligibility and terms of coverage. In cases where the plan includes coverage for drugs prescribed for obesity treatment or weight management, the Oscar Clinical Guideline: Weight Loss Agents (PG070) may also apply.

Farxiga (Dapagliflozin)

  • To reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression.
  • To reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure.
  • To reduce the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors.
  • As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Inpefa (sotagliflozin)

to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visit in adults with heart failure or

  • Type 2 diabetes mellitus, chronic kidney disease, and other cardiovascular risk factors
  • As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Invokana (Canagliflozin)

to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke) in adults with type 2 diabetes mellitus

and established cardiovascular disease (CVD).

to reduce the risk of end doubling of serum creatinine, stage kidney disease (ESKD), cardiovascular (CV) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day.

Jardiance (Empagliflozin)

  1. To reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure.
  2. To reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease.
  3. As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Steglatro (Ertugliflozin)

As an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

Definitions

"Insulin" is a hormone produced by the beta cells in the pancreas. It facilitates the entry of glucose into cells for energy production. Insufficient insulin leads to a high blood glucose level, a condition known as diabetes. Oral and injectable medications can help increase insulin production, enhance the body's sensitivity to insulin, and decrease blood sugar levels.

"Type 1 Diabetes" is an autoimmune condition where the pancreas's beta cells are unable to produce sufficient insulin, leading to elevated blood glucose levels. Patients with Type 1 diabetes often require daily insulin injections to regulate their blood glucose.

"Type 2 Diabetes" is a metabolic disorder characterized by insufficient insulin production or insulin resistance in the body cells. It is more common than Type 1 and often managed through lifestyle changes, non-insulin medications, and, if necessary, insulin injections.

"Blood Glucose" is the primary sugar found in the bloodstream, serving as the body's main energy source. Chronic high blood glucose levels can lead to complications from blood vessel damage.

"Hemoglobin A1c (HbA1c)" is a blood test that measures average blood glucose levels over the past 2 to 3 months. It is also referred to as the A1C or glycosylated hemoglobin test. Various factors, such as age, ethnicity, certain conditions, and pregnancy, can affect A1C results.

"Hyperglycemia" is the medical term for high blood glucose. It can occur due to inadequate fasting (fasting hyperglycemia) or post-meal (postprandial hyperglycemia).

"Hypoglycemia" is a condition characterized by abnormally low blood glucose, typically less than 70 mg/dL. Symptoms include hunger, nervousness, dizziness, confusion, and in severe cases, unconsciousness. Immediate treatment involves consuming carbohydrate-rich foods or using injectable glucagon for severe cases.

"Cardiovascular Disease" refers to a class of diseases involving the heart and blood vessels. It is a common complication in individuals with long-term Type 2 diabetes and is often a key consideration when selecting an appropriate diabetes medication.

Clinical Indications

The Plan considers Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors & Antidiabetic Combinations medically necessary when ALL the following criteria are met for the applicable indication or agent listed below:

For Type 2 Diabetes Mellitus:

Medical Necessity Criteria for Authorization

The Plan considers Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors & Antidiabetic Combinations medically necessary when ALL the following criteria are met:

Medical Necessity Criteria for Authorization

The medication is age-appropriate for the member as per the FDA-approved indications; AND

  1. The member has a diagnosis of type 2 diabetes mellitus based on at least ONE of the following diagnostic criteria:
    • A fasting glucose level of greater than 126 mg/dL; and/or
    • A 2-hour glucose tolerance test result of greater than 200 mg/dL.; and/or
    • Hemoglobin A1c ">=6.5%; and/or
    • Symptoms of hyperglycemia plus a random plasma glucose ">=200 mg/dL;
  2. NOTE: Abnormal results must be confirmed on a second occasion unless they are unequivocal.
  3. The member has ONE of the following:
    • is unable to use, or has adequately tried and failed metformin at a minimum dose of 1500 milligrams daily for 90 days⇅; or
    • requires combination therapy AND has an A1c (hemoglobin A1c) of 7.5 percent or greater; or
    • has established cardiovascular disease, AND the request is for ONE of the following:
      1. Farxiga (dapagliflozin); or
      2. Inpefa (sotagliflozin); or
      3. Invokana (canagliflozin); or
      4. Jardiance (empagliflozin); or
    • has diabetic nephropathy with albuminuria greater than 300 mg per day, AND the request is for Invokana (canagliflozin); or
    • has multiple cardiovascular risk factors, AND the request is for Farxiga (dapagliflozin) or Inpefa (sotagliflozin); or
    • has New York Heart Association (NYHA) Class II-IV heart failure and the request is for ONE of the following:
      1. Farxiga (dapagliflozin); or
      2. Inpefa (sotagliflozin); or
      3. Jardiance (empagliflozin); or
    • has chronic kidney disease at risk of progression, AND BOTH of the following:
      1. The request is for Farxiga (dapagliflozin) or Inpefa (sotagliflozin); and
      2. The member has ONE of the following:
        1. an estimated glomerular filtration rate (eGFR) of 25 to 75 mL/min/1.73m2; or
        2. an estimated glomerular filtration rate (eGFR) less than 25 mL/min/1.73m2 AND this is a continuation of therapy;
    • has been receiving the requested drug for at least 3 months, AND one of the following:
      • has demonstrated a reduction in A1c (hemoglobin A1c) since starting this therapy; or
      • has established cardiovascular disease, AND the request is for ONE of the following:
        1. Farxiga (dapagliflozin); or
        2. Inpefa (sotagliflozin); or
        3. Invokana (canagliflozin); or
        4. Jardiance (empagliflozin); or
      • has diabetic nephropathy with albuminuria greater than 300 mg per day, AND the request is for Invokana (canagliflozin); or
      • has multiple cardiovascular risk factors, AND the request is for Farxiga (dapagliflozin) or Inpefa (sotagliflozin); or
      • has New York Heart Association (NYHA) Class II-IV heart failure and the request is for ONE of the following:
        1. Farxiga (dapagliflozin); or
        2. Inpefa (sotagliflozin); or
        3. Jardiance (empagliflozin); or
      • has chronic kidney disease at risk of progression, AND BOTH of the following:
        • The request is for Farxiga (dapagliflozin) or Inpefa (sotagliflozin); and
        • The member has ONE of the following:
          1. an estimated glomerular filtration rate (eGFR) of 25 to 75 mL/min/1.73m2; or
          2. an estimated glomerular filtration rate (eGFR) less than 25 mL/min/1.73m2 AND this is a continuation of therapy;
      If the above prior authorization criteria are met, the requested drug will be approved for 12 months.
For Chronic Kidney Disease:

Medical Necessity Criteria for Authorization

The Plan considers Farxiga (dapagliflozin) or Inpefa (sotagliflozin) medically necessary when BOTH of the following criteria are met:

  1. The member has chronic kidney disease at risk of progression; AND
  2. The member has ONE of the following:
    • an estimated glomerular filtration rate (eGFR) of 25 to 75 mL/min/1.73m2; or
    • an estimated glomerular filtration rate (eGFR) less than 25 mL/min/1.73m2 AND this is a continuation of therapy.

If the above prior authorization criteria are met, the requested drug will be approved for 12 months.

For Heart Failure:

Medical Necessity Criteria for Authorization

The Plan considers Farxiga (dapagliflozin), Jardiance (Empagliflozin), or Inpefa (sotagliflozin) medically necessary when the member has New York Heart Association (NYHA) Class II-IV heart failure.

If the above prior authorization criteria are met, the requested drug will be approved for 12 months.

Experimental or Investigational / Not Medically Necessary

Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors & Antidiabetic Combinations for any other indication is considered not medically necessary by the Plan, as it is deemed to be experimental, investigational, or unproven.

Appendix

Metformin in Type 2 Diabetes ⇅

The recommendation for a minimum effective dose of 1500 milligrams daily of metformin is derived from clinical findings which show that this dosage effectively regulates both fasting blood glucose and glycosylated hemoglobin levels - crucial markers of long-term glucose control.

Metformin functions by decreasing glucose production in the liver and enhancing insulin sensitivity in both the liver and peripheral tissues. This enhancement in turn improves the uptake and usage of glucose.

The efficacy of metformin is dose-dependent, with the most clinically meaningful responses usually not seen at doses below 1500 milligrams per day. The strategy of starting metformin treatment at a lower dose and gradually stepping up the dose over time (typically over a period of weeks) is useful in reducing the occurrence and intensity of gastrointestinal side effects. These side effects are the most common adverse reactions linked with metformin therapy and can include symptoms such as nausea, vomiting, diarrhea, abdominal cramping, and bloating. Commencing therapy at a lower dose (for instance, 500 mg twice daily or 850 mg once daily) and progressively increasing the dosage over time allows patients to better tolerate metformin. This results in improved medication adherence and ultimately, superior glycemic control.

  • For patients who need further glycemic control beyond what can be achieved with a total daily dose of 2000 mg, the dosage of metformin can be boosted up to a maximum of 2550 mg per day, given in divided doses. This upper limit is based on clinical trials that show doses above this level do not provide an additional glycemic control benefit but may increase the risk of adverse effects.
  • For pediatric patients, the same principle of beginning at a lower dose and incrementally increasing applies, with a maximum limit of 2000 mg per day given in divided doses.

Table 2: Metformin in Diabetes Treatment

Clinical ConsiderationRecommendation
Understanding MetforminMetformin is frequently used due to its efficacy, cost-effectiveness, and cardiovascular benefits. However, GI adverse effects are common and could limit its use.
Managing Patient ExpectationsInform patients that side effects are often temporary and encourage patience during the dosage adjustment period.
Choosing Metformin TypeExtended-release (ER) versions are generally preferred due to fewer daily doses and reduced discontinuation rates. However, consider cost and insurance coverage.
Initiating MetforminStart at a low dose (500 mg for ER/IR or 250 mg for those with GI intolerance history). Consider using liquid formulations or single-ingredient products for easier titration.
Dosage IncreaseGradually up titrate dosage every one to two weeks. Decrease back to the last tolerated dose if GI symptoms occur, and then try to increase more slowly.
Dosage Titration (Adults)Dosage may be increased by 500 mg at weekly intervals until desired response or a maximum dosage is reached (2.55 g daily for immediate-release, 2.5 g for certain extended-release tablets, and 2 g for others).
Dosage Titration (Children 10-16 years)Dosage may be increased by 500 mg at weekly intervals until desired response or a maximum dosage of 2 g daily in 2 divided doses is reached.
Maximizing ToleranceAdvice patients to take metformin during or immediately after meals. Consider dividing doses if tolerability is an issue.
Addressing ComplaintsManage common complaints such as diarrhea and nausea by temporary dose reduction. If odor of the drug is a problem, consider switching brands or generics.
GI Tolerance IssuesIf GI symptoms persist, consider using 5-HT3-antagonists like ondansetron or treating underlying Helicobacter pylori infection.

Insufficient Dose Tolerance
Even lower doses can improve glucose control. Consider combining metformin with another agent if necessary.

Interrupted Therapy
If therapy is interrupted, consider a full titration when restarting. Lower the dose and increase slowly if adverse effects occur upon restarting.

References

  1. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Obstetrics. ACOG Practice Bulletin No. 190: Gestational diabetes mellitus. Obstet Gynecol. 2018;131(2):e49-e64.
  2. American College of Obstetricians and Gynecologists (ACOG). ACOG Practice Bulletin No. 201: Pregestational diabetes mellitus. Obstet Gynecol. 2018;132(6):e228-e248. doi:10.1097/AOG.0000000000002960
  3. American Diabetes Association (ADA). Standards of medical care in diabetes–2021. Diabetes Care. 2021;44(suppl 1):S1-S232.
  4. American Diabetes Association (ADA). Standards of medical care in diabetes–2021. Diabetes Care. 2021;44(suppl 1):S1-S232. https://care-diabetesjournals-org.libproxy.unm.edu/content/44/Supplement_1. Accessed January 13, 2021.
  5. American Diabetes Association Professional Practice Committee, Draznin, B., Aroda, V. R., Bakris, G., Benson, G., Brown, F. M., Freeman, R., Green, J., Huang, E., Isaacs, D., Kahan, S., Leon, J., Lyons, S. K., Peters, A. L., Prahalad, P., Reusch, J., & Young-Hyman, D. (2022). 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes- 2022.
  1. Diabetes care, 45(Suppl 1), S125–S143. https://doi.org/10.2337/dc22-S0096.
  2. AstraZeneca. Qtern® (dapagliflozin and saxagliptin) tablets prescribing information. Wilmington, DE; 2020 Jan.
  3. Bhatt DL, Szarek M, Pitt B, et al; SCORED Investigators. Sotagliflozin in patients with diabetes and chronic kidney disease. N Engl J Med. 2021a;384(2):129-139. doi:10.1056/NEJMoa20301868.
  4. Bhatt DL, Szarek M, Steg PG, et al; SOLOIST-WHF Trial Investigators. Sotagliflozin in patients with diabetes and recent worsening heart failure. N Engl J Med. 2021b;384(2):117-128. doi:10.1056/NEJMoa20301839.
  5. Blumer I, Hadar E, Hadden DR, et al. Diabetes and pregnancy: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2013;98(11):4227-4249.
  6. Brenzavvy (bexagliflozin) [prescribing information]. Marlborouth, MA: TheracosBio LLC; January 2023.
  7. Davies MJ, D'Alessio DA, Fradkin J, et al. Management of hyperglycemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2018;41(12):2669-2701. doi:10.2337/dci18-0033
  8. Farxiga (dapagliflozin) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; April 2021.
  9. Garber AJ, Handelsman Y, Grunberger G et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm 2020 executive summary. Endocr Pract. 2020; 26:107-139. [PubMed 32022600]
  10. Glucophage (metformin) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; May 2018.
  11. Glucophage XR (metformin) [prescribing information]. Princeton, NJ: Bristol-Myers Squibb; May 2018.
  12. Glumetza (metformin) [prescribing information]. Bridgewater, NJ: Salix Pharmaceuticals; October 2019.
  13. Glyxambi (empagliflozin/linagliptin) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; March 2022.
  14. Handelsman Y, Henry RR, Bloomgarden ZT, et al. American Association of Clinical Endocrinologists and American College of Endocrinology position statement on the association of SGLT-2 inhibitors and diabetic ketoacidosis. Endocr Pract. 2016;22(6):753-762. doi:10.4158/EP161292.PS
  15. Heidenreich PA, Bozkurt B, Aguilar D, et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines. Circulation. 2022;145(18):e895-e1032. doi:10.1161/CIR.0000000000001063
  16. Inpefa (sotagliflozin) [prescribing information]. The Woodlands, TX: Lexicon Pharmaceuticals, Inc; May 2023.
  17. Invokamet (canagliflozin and metformin) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals Inc; November 2021.
  18. Invokamet XR (canagliflozin and metformin) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals Inc; November 2021.
  19. Invokana (canagliflozin) [prescribing information]. Titusville, NJ: Janssen Pharmaceuticals; November 2021.
  20. Jardiance (empagliflozin) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; August 2021.
  21. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease. Kidney Int. 2020;98(supp 4):S1-S115. doi:10.1016/j.kint.2020.06.019
  22. LeRoith D, Biessels GJ, Braithwaite SS, et al. Treatment of diabetes in older adults: an Endocrine Society* clinical practice guideline. J Clin Endocrinol Metab. 2019;104(5):1520-1574. doi:10.1210/jc.2019-00198
  23. Mechanick JI, Apovian C, Brethauer S, et al. Clinical practice guidelines for the perioperative nutrition, metabolic, and nonsurgical support of patients undergoing bariatric procedures -2019 update: cosponsored by American Association of Clinical Endocrinologists/American College of Endocrinology, The Obesity Society, American Society for Metabolic & Bariatric Surgery, Obesity Medicine Association, and American Society of Anesthesiologists. Surg Obes Relat Dis. 2020;16(2):175-247. doi:10.1016/j.soard.2019.10.025
  24. Qtern (dapagliflozin and saxagliptin) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; March 2022.
  25. Qternmet XR (dapagliflozin, saxagliptin, and metformin hydrochloride) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; January 2020.
  26. Segluromet (ertugliflozin and metformin) [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; September 2021.
  27. Steglatro (ertugliflozin) [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; September 2021.
  28. Steglujan (ertugliflozin/sitagliptin) [prescribing information]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; September 2021.
  29. Synjardy (empagliflozin/metformin) [prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; March 2022.

Synjardy XR (empagliflozin/metformin)

[prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; March 2022.

Trijardy XR (empagliflozin/linagliptin/metformin)

[prescribing information]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals Inc; June 2021.

Victoza (liraglutide)

[prescribing information]. Plainsboro, NJ: Novo Nordisk Inc; December 2021.337.

Xigduo XR (dapagliflozin and metformin)

[prescribing information]. Wilmington, DE: AstraZeneca; April 2022.

Clinical Guideline Revision / History Information

Original Date: 6/29/2023

Reviewed/Revised: 7/31/2023, 9/21/2023