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
- abdominal pain
- anaphylactoid reactions
- angioedema
- arthralgia
- balanitis
- bronchospasm
- bullous rash
- candidiasis
- cholestasis
- constipation
- cough
- cystitis
- dehydration
- diabetic ketoacidosis
- diarrhea
- diuresis
- elevated hepatic enzymes
- exfoliative dermatitis
- flatulence
- folate deficiency
- headache
- heart failure
- hepatitis
- hypercholesterolemia
- hyperlipidemia
- hypoglycemia
- hypotension
- hypovolemia
- increased urinary frequency
- infection
- lactic acidosis
- malaise
- megaloblastic anemia
- metabolic acidosis
- myalgia
- nausea
- necrotizing fasciitis
- nocturia
- oral ulceration
- orthostatic hypotension
- pancreatitis
- pemphigus
- pharyngitis
- phimosis
- polydipsia
- polyuria
- rash
- renal failure (unspecified)
- rhabdomyolysis
- stomatitis
- tissue necrosis
- urticaria
- vaginitis
- vitamin B12 deficiency
- vomiting
- 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
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- Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
- Aliskiren; Hydrochlorothiazide, HCTZ
- Aliskiren; Valsartan
- Amiloride
- Amiloride; Hydrochlorothiazide, HCTZ
- Aminosalicylate sodium, Aminosalicylic acid
- Amlodipine
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- Amlodipine; Benazepril
- Amlodipine; Celecoxib
- Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan
- Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan
- Amlodipine; Olmesartan
- Amlodipine; Telmisartan
- Amlodipine; Valsartan
- Amobarbital
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- Aspirin, ASA; Caffeine; Orphenadrine
- Aspirin, ASA; Carisoprodol
- Aspirin, ASA; Carisoprodol; Codeine
- Aspirin, ASA; Citric Acid; Sodium Bicarbonate
- Aspirin, ASA; Dipyridamole
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- Aspirin, ASA; Oxycodone
- Aspirin, ASA; Pravastatin
- Atazanavir
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- atypical antipsychotic
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- Chlorpheniramine; Dihydrocodeine; Phenylephrine
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- Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine
- Chlorpheniramine; Hydrocodone; Phenylephrine
- Chlorpheniramine; Hydrocodone; Pseudoephedrine
- Chlorpheniramine; Phenylephrine
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- Elagolix; Estradiol; Norethindrone acetate
- Elbasvir; Grazoprevir
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- 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
- Erythromycin; Sulfisoxazole
- Esmolol
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- Esterified Estrogens; Methyltestosterone
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- Estradiol Cypionate; Medroxyprogesterone
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- Estropipate
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- 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
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- Etravirine
- Famotidine
- Famotidine; Ibuprofen
- Felodipine
- Fenofibrate
- Fenofibric Acid
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- Fluticasone; Salmeterol
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- Fluticasone; Vilanterol
- Formoterol; Mometasone
- Fosamprenavir
- Fosinopril
- Fosinopril; Hydrochlorothiazide, HCTZ
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- 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
- Insulin Glargine; Lixisenatide
- Insulin Glulisine
- Insulin Lispro
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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
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- Lamivudine, 3TC; Zidovudine, ZDV
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- Lamotrigine
- Lanreotide
- Ledipasvir; Sofosbuvir
- Lente Insulin
- Leuprolide; Norethindrone
- Levobetaxolol
- Levobunolol
- Levomefolate
- Levonorgestrel
- Levothyroxine
- Levothyroxine; Liothyronine (Porcine)
- Levothyroxine; Liothyronine (Synthetic)
- Linezolid
- Liothyronine
- Lisdexamfetamine
- Lisinopril
- Lithium
- Lomefloxacin
- Loop diuretics
- Lopinavir; Ritonavir
- Loratadine; Pseudoephedrine
- Lorcaserin
- Losartan
- Lovastatin; Niacin
- Magnesium Salicylate
- Mecasermin rinfabate
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- Medroxyprogesterone
- Meglitinides
- Memantine
- Mephobarbital
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- Metformin; Repaglinide
- Methamphetamine
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- Midodrine
- Modafinil
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- Phentermine
- Phentermine; Topiramate
- Phenylephrine
- Phenylephrine; Promethazine
- Phenytoin
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- Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
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- Regular Insulin
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- Repaglinide
- Reserpine
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- Ritodrine
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- Saquinavir
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- tobacco
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