Empagliflozin Linagliptin Metformin

Empagliflozin Linagliptin Metformin Brand Name– Trijardy XR

What is Empagliflozin Linagliptin Metformin

Empagliflozin Linagliptin Metformin is a combination oral extended-release product containing a sodium-glucose cotransporter 2 (SGLT2) inhibitor, a dipeptidyl peptidase-4 (DPP-4) inhibitor, and a biguanide antidiabetic agent.

The combination product is indicated for adults with type 2 diabetes mellitus (DM).

When used together, the combination results in further mean hemoglobin A1C reductions, which may help patients achieve target A1C goals. Empagliflozin alone has cardiovascular (CV) risk-reduction benefits.

Empagliflozin significantly reduced the risk of major adverse cardiovascular events (MACE: CV death, the first occurrence of non-fatal myocardial infarction, or non-fatal stroke) by 14% relative to placebo (HR 0.86, 95% CI 0.74 to 0.99).

The trial data supported the FDA approval of empagliflozin to reduce the risk of CV death in adults with type 2 DM and concurrent CV disease; however, the empagliflozin; linagliptin; metformin products are not FDA-approved for this indication.

As with other SGLT2 inhibitor/metformin combinations, this product should not be used in patients with severe renal impairment as empagliflozin efficacy is reduced, and the risk of metformin-related lactic acidosis is increased.

Metformin is usually first-line in the treatment of type 2 DM. Additional therapy with an SGLT2 inhibitor with evidence of reducing HF (heart failure) and/or chronic kidney disease (CKD) progression should be considered in patients with indicators of high-risk or established CKD or HF, independent of baseline A1C or individualized A1C target.

SGLT2 inhibitors with proven CV-risk reduction, like empagliflozin, are also an alternative treatment option in DM patients with indicators of high-risk or established CV disease who cannot tolerate a glucagon-like peptide-1 receptor agonist (GLP-1 RA).

The DPP-4 inhibitors, like linagliptin, are well tolerated, have a neutral effect on weight, and have minimal risk of hypoglycemia.

This combination product was FDA-approved in January 2020.

Indications

  • type 2 diabetes mellitus

For the treatment of type 2 diabetes mellitus in combination with diet and exercise

Side Effects

  1. abdominal pain
  2. anaphylactoid reactions
  3. angioedema
  4. arthralgia
  5. balanitis
  6. bronchospasm
  7. bullous rash
  8. candidiasis
  9. cholestasis
  10. constipation
  11. cough
  12. cystitis
  13. dehydration
  14. diabetic ketoacidosis
  15. diarrhea
  16. diuresis
  17. elevated hepatic enzymes
  18. exfoliative dermatitis
  19. flatulence
  20. folate deficiency
  21. headache
  22. heart failure
  23. hepatitis
  24. hypercholesterolemia
  25. hyperlipidemia
  26. hypoglycemia
  27. hypotension
  28. hypovolemia
  29. increased urinary frequency
  30. infection
  31. lactic acidosis
  32. malaise
  33. megaloblastic anemia
  34. metabolic acidosis
  35. myalgia
  36. nausea
  37. necrotizing fasciitis
  38. nocturia
  39. oral ulceration
  40. orthostatic hypotension
  41. pancreatitis
  42. pemphigus
  43. pharyngitis
  44. phimosis
  45. polydipsia
  46. polyuria
  47. rash
  48. renal failure (unspecified)
  49. rhabdomyolysis
  50. stomatitis
  51. tissue necrosis
  52. urticaria
  53. vaginitis
  54. vitamin B12 deficiency
  55. vomiting
  56. weight loss

Monitoring Parameters

  • blood glucose
  • CBC
  • glycosylated hemoglobin A1c (HbA1c)
  • LFTs
  • serum cholesterol profile
  • serum creatinine/BUN

Contraindications

  • acidemia
  • acute heart failure
  • acute myocardial infarction
  • adrenal insufficiency
  • alcoholism
  • arthralgia
  • balanitis
  • breast-feeding
  • burns
  • cardiac disease
  • cardiogenic shock
  • children
  • dehydration
  • diabetic ketoacidosis
  • dialysis
  • diarrhea
  • ethanol ingestion
  • ethanol intoxication
  • exfoliative dermatitis
  • fever
  • gastroparesis
  • geriatric
  • GI obstruction
  • heart failure
  • hepatic disease
  • history of angioedema
  • hypercortisolism
  • hyperglycemia
  • hyperthyroidism
  • hypoglycemia
  • hypotension
  • hypothyroidism
  • hypovolemia
  • hypoxemia
  • ileus
  • infants
  • infection
  • laboratory test interference
  • lactic acidosis
  • malnutrition
  • metabolic acidosis
  • pancreatitis
  • pernicious anemia
  • pituitary insufficiency
  • polycystic ovary syndrome
  • pregnancy
  • pyelonephritis
  • radiographic contrast administration
  • renal disease
  • renal failure
  • renal impairment
  • sepsis
  • serious rash
  • surgery
  • tissue necrosis
  • trauma
  • type 1 diabetes mellitus
  • urinary tract infection (UTI)
  • vaginitis
  • vomiting

Interactions

  • Abacavir; Dolutegravir; Lamivudine
  • Abacavir; Lamivudine, 3TC
  • Abacavir; Lamivudine, 3TC; Zidovudine, ZDV
  • Acebutolol
  • Acetaminophen; Aspirin, ASA; Caffeine
  • Acetaminophen; Butalbital
  • Acetaminophen; Butalbital; Caffeine
  • Acetaminophen; Butalbital; Caffeine; Codeine
  • Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
  • Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
  • Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
  • Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
  • Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine
  • Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
  • Acetaminophen; Dextromethorphan; Phenylephrine
  • Acetaminophen; Dextromethorphan; Pseudoephedrine
  • Acetaminophen; Dichloralphenazone; Isometheptene
  • Acetaminophen; Guaifenesin; Phenylephrine
  • Acetaminophen; Propoxyphene
  • Acetaminophen; Pseudoephedrine
  • Acetazolamide
  • Acetohexamide
  • Acrivastine; Pseudoephedrine
  • Adefovir
  • Aliskiren; Amlodipine
  • Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
  • Aliskiren; Hydrochlorothiazide, HCTZ
  • Aliskiren; Valsartan
  • Amiloride
  • Amiloride; Hydrochlorothiazide, HCTZ
  • Aminosalicylate sodium, Aminosalicylic acid
  • Amlodipine
  • Amlodipine; Atorvastatin
  • Amlodipine; Benazepril
  • Amlodipine; Celecoxib
  • Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan
  • Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan
  • Amlodipine; Olmesartan
  • Amlodipine; Telmisartan
  • Amlodipine; Valsartan
  • Amobarbital
  • Amoxicillin; Clarithromycin; Lansoprazole
  • Amoxicillin; Clarithromycin; Omeprazole
  • Amphetamine
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  • Aspirin, ASA
  • Aspirin, ASA; Butalbital; Caffeine
  • Aspirin, ASA; Butalbital; Caffeine; Codeine
  • Aspirin, ASA; Caffeine; Dihydrocodeine
  • Aspirin, ASA; Caffeine; Orphenadrine
  • Aspirin, ASA; Carisoprodol
  • Aspirin, ASA; Carisoprodol; Codeine
  • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
  • Aspirin, ASA; Dipyridamole
  • Aspirin, ASA; Omeprazole
  • Aspirin, ASA; Oxycodone
  • Aspirin, ASA; Pravastatin
  • Atazanavir
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  • Atenolol
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  • atypical antipsychotic
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  • Benzphetamine
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  • Budesonide
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  • Carbetapentane; Phenylephrine; Pyrilamine
  • Carbetapentane; Pseudoephedrine
  • Carbinoxamine; Dextromethorphan; Pseudoephedrine
  • Carbinoxamine; Hydrocodone; Phenylephrine
  • Carbinoxamine; Hydrocodone; Pseudoephedrine
  • Carbinoxamine; Phenylephrine
  • Carbinoxamine; Pseudoephedrine
  • Carbonic anhydrase inhibitors
  • Carteolol
  • Carvedilol
  • Cephalexin
  • Cetirizine; Pseudoephedrine
  • Chlophedianol; Dexchlorpheniramine; Pseudoephedrine
  • Chlophedianol; Guaifenesin; Phenylephrine
  • Chloroquine
  • Chlorothiazide
  • Chlorpheniramine; Dextromethorphan; Phenylephrine
  • Chlorpheniramine; Dihydrocodeine; Phenylephrine
  • Chlorpheniramine; Dihydrocodeine; Pseudoephedrine
  • Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine
  • Chlorpheniramine; Hydrocodone; Phenylephrine
  • Chlorpheniramine; Hydrocodone; Pseudoephedrine
  • Chlorpheniramine; Phenylephrine
  • Chlorpheniramine; Pseudoephedrine
  • Chlorpropamide
  • Chlorthalidone
  • Chlorthalidone; Clonidine
  • Choline Salicylate; Magnesium Salicylate
  • Chromium
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  • Codeine; Phenylephrine; Promethazine
  • Colesevelam
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  • Deflazacort
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  • Drospirenone
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  • Drospirenone; Ethinyl Estradiol
  • Drospirenone; Ethinyl Estradiol; Levomefolate
  • Efavirenz
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  • Elagolix; Estradiol; Norethindrone acetate
  • Elbasvir; Grazoprevir
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
  • Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
  • Emtricitabine
  • Emtricitabine; Rilpivirine; Tenofovir alafenamide
  • Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate
  • Emtricitabine; Tenofovir alafenamide
  • Emtricitabine; Tenofovir disoproxil fumarate
  • Enalapril, Enalaprilat
  • Enalapril; Felodipine
  • Enalapril; Hydrochlorothiazide, HCTZ
  • Entecavir
  • Ephedrine
  • Epinephrine
  • Eprosartan
  • Eprosartan; Hydrochlorothiazide, HCTZ
  • Erdafitinib
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  • Estradiol; Norgestimate
  • Estradiol; Progesterone
  • Estramustine
  • Estrogens
  • Estropipate
  • Ethacrynic Acid
  • Ethanol
  • Ethinyl Estradiol
  • Ethinyl Estradiol; Desogestrel
  • Ethinyl Estradiol; Ethynodiol Diacetate
  • Ethinyl Estradiol; Etonogestrel
  • Ethinyl Estradiol; Levonorgestrel
  • Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate
  • Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate
  • Ethinyl Estradiol; Norelgestromin
  • Ethinyl Estradiol; Norethindrone
  • Ethinyl Estradiol; Norethindrone Acetate
  • Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate
  • Ethinyl Estradiol; Norethindrone; Ferrous fumarate
  • Ethinyl Estradiol; Norgestimate
  • Ethinyl Estradiol; Norgestrel
  • Ethotoin
  • Etonogestrel
  • Etravirine
  • Famotidine
  • Famotidine; Ibuprofen
  • Felodipine
  • Fenofibrate
  • Fenofibric Acid
  • Fexofenadine; Pseudoephedrine
  • Fibric acid derivatives
  • Fludrocortisone
  • Flunisolide
  • Fluoxetine
  • Fluoxetine; Olanzapine
  • Fluoxymesterone
  • Fluticasone
  • Fluticasone; Salmeterol
  • Fluticasone; Umeclidinium; Vilanterol
  • Fluticasone; Vilanterol
  • Formoterol; Mometasone
  • Fosamprenavir
  • Fosinopril
  • Fosinopril; Hydrochlorothiazide, HCTZ
  • Fosphenytoin
  • Furosemide
  • Gadoterate meglumine
  • Garlic, Allium sativum
  • Gemfibrozil
  • Glecaprevir; Pibrentasvir
  • Glimepiride
  • Glimepiride; Pioglitazone
  • Glimepiride; Rosiglitazone
  • Glipizide
  • Glipizide; Metformin
  • Glyburide
  • Glyburide; Metformin
  • Glycopyrrolate
  • Glycopyrrolate; Formoterol
  • Green Tea
  • Guaifenesin; Hydrocodone; Pseudoephedrine
  • Guaifenesin; Phenylephrine
  • Guaifenesin; Pseudoephedrine
  • Hydantoins
  • Hydralazine; Hydrochlorothiazide, HCTZ
  • Hydrochlorothiazide, HCTZ
  • Hydrochlorothiazide, HCTZ; Irbesartan
  • Hydrochlorothiazide, HCTZ; Lisinopril
  • Hydrochlorothiazide, HCTZ; Losartan
  • Hydrochlorothiazide, HCTZ; Methyldopa
  • Hydrochlorothiazide, HCTZ; Metoprolol
  • Hydrochlorothiazide, HCTZ; Moexipril
  • Hydrochlorothiazide, HCTZ; Olmesartan
  • Hydrochlorothiazide, HCTZ; Propranolol
  • Hydrochlorothiazide, HCTZ; Quinapril
  • Hydrochlorothiazide, HCTZ; Spironolactone
  • Hydrochlorothiazide, HCTZ; Telmisartan
  • Hydrochlorothiazide, HCTZ; Triamterene
  • Hydrochlorothiazide, HCTZ; Valsartan
  • Hydrocodone; Phenylephrine
  • Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine
  • Hydrocodone; Pseudoephedrine
  • Hydrocortisone
  • Hydroxychloroquine
  • Hydroxyprogesterone
  • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
  • Ibuprofen; Pseudoephedrine
  • Indacaterol; Glycopyrrolate
  • Indapamide
  • Indinavir
  • Insulin Aspart
  • Insulin Aspart; Insulin Aspart Protamine
  • Insulin Degludec
  • Insulin Degludec; Liraglutide
  • Insulin Detemir
  • Insulin Glargine
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  • Insulin Glulisine
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  • Insulin, Inhaled
  • Insulins
  • Iodipamide Meglumine
  • Ionic Contrast Media
  • Ioxaglate Meglumine; Ioxaglate Sodium
  • Irbesartan
  • Isocarboxazid
  • Isoniazid, INH; Pyrazinamide, PZA; Rifampin
  • Isoniazid, INH; Rifampin
  • Isophane Insulin (NPH)
  • Isoproterenol
  • Isradipine
  • Labetalol
  • Lamivudine, 3TC
  • Lamivudine, 3TC; Zidovudine, ZDV
  • Lamivudine; Tenofovir Disoproxil Fumarate
  • Lamotrigine
  • Lanreotide
  • Ledipasvir; Sofosbuvir
  • Lente Insulin
  • Leuprolide; Norethindrone
  • Levobetaxolol
  • Levobunolol
  • Levomefolate
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  • Levothyroxine
  • Levothyroxine; Liothyronine (Porcine)
  • Levothyroxine; Liothyronine (Synthetic)
  • Linezolid
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  • Lithium
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  • Phendimetrazine
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  • Phentermine
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  • Phenylephrine
  • Phenylephrine; Promethazine
  • Phenytoin
  • Pindolol
  • Potassium-sparing diuretics
  • Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
  • Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
  • Prednisolone
  • Prednisone
  • Prilocaine; Epinephrine
  • Primidone
  • Progesterone
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  • Racepinephrine
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  • Regular Insulin
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  • Repaglinide
  • Reserpine
  • Rifabutin
  • Rifampin
  • Ritodrine
  • Ritonavir
  • Sacubitril; Valsartan
  • Salicylates
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  • Saquinavir
  • Secobarbital
  • Segesterone Acetate; Ethinyl Estradiol
  • Selegiline
  • Sofosbuvir
  • Sofosbuvir; Velpatasvir
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  • Somatropin, rh-GH
  • Sotalol
  • Sparfloxacin
  • Spironolactone
  • St. John’s Wort, Hypericum perforatum
  • Sulfadiazine
  • Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole
  • Sulfasalazine
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  • Sulfonamides
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  • Sympathomimetics
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  • Testolactone
  • Testosterone
  • Thiazide diuretics
  • Thiopental
  • Thyroid hormones
  • Timolol
  • Tipranavir
  • tobacco
  • Tolazamide
  • Tolbutamide
  • Topiramate
  • Torsemide
  • Trandolapril
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  • Tranylcypromine
  • Triamcinolone
  • Triamterene
  • Trospium
  • Trovafloxacin, Alatrofloxacin
  • Ultralente Insulin
  • Valsartan
  • Vandetanib
  • Verapamil
  • Zonisamide
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