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This webpage is intended for GPs, Nurses and Diabetes Specialists with an interest in type 2 diabetes.

Type 2 diabetes management support

Prescribing information and adverse event reporting can be found at the bottom of this webpage

The importance of individualising HbA1c targets in type 2 diabetes

Watch an animation that outlines the importance of taking a patient-centred approach to glycaemic target setting in type 2 diabetes.

trajenta bmj

TRAJENTA® - licensed for use with metformin and empagliflozin1

TRAJENTA® (linagliptin) is indicated in adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control as:

  • monotherapy - when metformin is inappropriate due to intolerance, or contraindicated due to renal impairment.
  • combination therapy - in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control (see sections 4.4, 4.5 and 5.1 of the Summary of Product Characteristics for available data on different combinations).

TRAJENTA® is the only DPP-4 inhibitor that does not require dose reduction based on renal function.1-5†

Key points relating to TRAJENTA® include:

  • One 5mg dose, once daily1
  • No dose reduction based on renal function1†
  • Proven efficacy (HbA1c) with the same dose regardless of renal function1,6-8

† Renal and other monitoring in patients with type 2 diabetes should be undertaken as per NICE clinical guidelines (CG182 CKD and NG28 T2DM).9,10

References

  1. TRAJENTA® (linagliptin) Summary of Product Characteristics 2017. Available at: https://www.medicines.org.uk/EMC/medicine/25000 (accessed March 2018).
  2. Januvia (sitagliptin) Summary of Product Characteristics. Available at: http://www.medicines.org.uk/EMC/medicine/19609 (accessed March 2018).
  3. Galvus (vildagliptin) Summary of Product Characteristics. Available at: http://www.medicines.org.uk/EMC/medicine/20734 (accessed March 2018).
  4. Onglyza (saxagliptin) Summary of Product Characteristics. Available at: http://www.medicines.org.uk/EMC/medicine/22315 (accessed March 2018).
  5. Vipidia (alogliptin▼) Summary of Product Characteristics. Available at: http://www.medicines.org.uk/EMC/medicine/28513 (accessed March 2018).
  6. Cooper M, et al. Poster No. 1068-P. The 71st Scientific Sessions of the American Diabetes Association, 24–28 June 2011, San Diego, CA, USA.
  7. McGill JB, et al. Diabetes Care 2013;36:237-244.
  8. Groop PH, et al. Poster No. 17-LB. The 76th Scientific Sessions of the American Diabetes Association, 10-14 June 2016, New Orleans, LA, USA.
  9. NICE guidance CG182. Available at https://www.nice.org.uk/Guidance/CG182 (accessed March 2018).
  10. NICE guidance NG28. Available at https://www.nice.org.uk/guidance/NG28 (accessed March 2018).

TRAJENTA® (Linagliptin)

Film-coated tablets containing 5 mg linagliptin. Indication: Trajenta is indicated in adults with type 2 diabetes mellitus as an adjunct to diet and exercise to improve glycaemic control as: monotherapy when metformin is inappropriate due to intolerance, or contraindicated due to renal impairment; combination therapy in combination with other medicinal products for the treatment of diabetes, including insulin, when these do not provide adequate glycaemic control. Dose and Administration: 5 mg once daily. If added to metformin, the dose of metformin should be maintained and linagliptin administered concomitantly. When used in combination with a sulphonylurea or with insulin, a lower dose of the sulphonylurea or insulin, may be considered to reduce the risk of hypoglycaemia. Renal impairment: no dose adjustment required. Hepatic impairment: pharmacokinetic studies suggest that no dose adjustment is required for patients with hepatic impairment but clinical experience in such patients is lacking. Elderly: no dose adjustment is necessary based on age however, clinical experience in patients > 80 years of age is limited and caution should be exercised when treating this population. Paediatric population: the safety and efficacy of linagliptin in children and adolescents has not yet been established. No data are available. Take the tablets with or without a meal at any time of the day. If a dose is missed, it should be taken as soon as possible but a double dose should not be taken on the same day. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Warnings and Precautions: Linagliptin should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. Caution is advised when linagliptin is used in combination with a sulphonylurea and/or insulin; a dose reduction of the sulphonylurea or insulin may be considered. Acute pancreatitis: In post-marketing experience of linagliptin there have been spontaneously reported adverse reactions of acute pancreatitis. Patients should be informed of the characteristic symptoms of acute pancreatitis. If pancreatitis is suspected, Trajenta should be discontinued; if acute pancreatitis is confirmed, Trajenta should not be restarted. Caution should be exercised in patients with a history of pancreatitis. Bullous pemphigoid: If bullous pemphigoid is suspected, Trajenta should be discontinued. Interactions: Linagliptin is a weak competitive and a weak to moderate mechanism-based inhibitor of CYP isozyme CYP3A4, but does not inhibit other CYP isozymes. It is not an inducer of CYP isozymes. Linagliptin is a P-glycoprotein substrate and inhibits P-glycoprotein mediated transport of digoxin with low potency. Based on these results and in vivo interaction studies, linagliptin is considered unlikely to cause interactions with other P-gp substrates. The risk for clinically meaningful interactions by other medicinal products on linagliptin is low and in clinical studies linagliptin had no clinically relevant effect on the pharmacokinetics of metformin, glibenclamide, simvastatin, warfarin, digoxin or oral contraceptives (please refer to Summary of Product Characteristics for information on clinical data). Fertility, pregnancy and lactation: Avoid use during pregnancy. A risk to the breast-fed child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from linagliptin therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. No studies on the effect on human fertility have been conducted for linagliptin. Undesirable effects: Adverse reactions reported in patients who received linagliptin 5 mg daily as monotherapy or as add-on therapies (frequencies identified from pooled analysis of placebo-controlled studies) in clinical trial and from post-marketing experience. The adverse reactions are listed by absolute frequency. Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (<1/10,000) or not known (cannot be estimated from the available data). Very common: hypoglycaemia (combination with/add-on to metformin and sulphonylurea). Common: lipase increased (monotherapy; combination with/add-on to metformin; combination with/add-on to metformin and sulphonylurea; combination with/add-on to insulin; combination with/add-on to metformin and empagliflozin). Uncommon: nasopharyngitis (monotherapy; combination with/add-on to metformin; combination with/add-on to insulin); hypersensitivity e.g. bronchial hyperreactivity (monotherapy; combination with/add-on to metformin; combination with/add-on to metformin and sulphonylurea; combination with/add-on to insulin); cough (monotherapy; combination with/add-on to metformin; combination with/add-on to insulin); pancreatitis (combination with/add-on to insulin); constipation (combination with/add-on to insulin); rash (monotherapy; combination with/add-on to metformin; combination with/add-on to metformin and sulphonylurea; combination with/add-on to insulin); amylase increased (combination with/add-on to metformin; combination with/add-on to metformin and sulphonylurea; combination with/add-on to metformin and empagliflozin). Rare: angioedema (monotherapy; combination with/add-on to metformin; combination with/add-on to metformin and sulphonylurea; combination with/add-on to insulin); urticaria (monotherapy; combination with/add-on to metformin; combination with/add-on to metformin and sulphonylurea; combination with/add-on to insulin); amylase increased (monotherapy). Not known: nasopharyngitis (combination with/add-on to metformin and sulphonylurea; combination with/add-on to metformin and empagliflozin); hypersensitivity e.g. bronchial hyperreactivity (combination with/add-on to metformin and empagliflozin); cough (combination with/add-on to metformin and sulphonylurea; combination with/add-on to metformin and empagliflozin); pancreatitis (monotherapy; combination with/add-on to metformin; combination with/add-on to metformin and sulphonylurea; combination with/add-on to metformin and empagliflozin); bullous pemphigoid (monotherapy; combination with/add-on to metformin; combination with/add-on to metformin and sulphonylurea; combination with/add-on to insulin); amylase increased (combination with/add-on to insulin). Prescribers should consult the Summary of Product Characteristics for further information on side effects. Pack sizes and NHS price: 28 tablets £33.26. Legal category: POM. MA number: EU/1/11/707/003. Marketing Authorisation Holder: Boehringer Ingelheim International GmbH, D-55216 Ingelheim am Rhein, Germany. Prescribers should consult the Summary of Product Characteristics for full prescribing information. Prepared in April 2017.

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard

Adverse events should also be reported to Boehringer Ingelheim Drug Safety on 0800 328 1627 (freephone).

▼JARDIANCE® (empagliflozin)

Film-coated tablets containing 10 mg or 25 mg empagliflozin.Indication: Jardiance is indicated for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise: as monotherapy when metformin is considered inappropriate due to intolerance; in addition to other medicinal products for the treatment of diabetes. For study results with respect to combinations, effects on glycaemic control and cardiovascular events, and the populations studied, refer to the Summary of Product Characteristics. Dose and Administration: The recommended starting dose is 10mg once daily. In patients tolerating empagliflozin 10 mg once daily who have eGFR ≥ 60 ml/min/1.73m2 and need tighter glycaemic control, the dose can be increased to 25 mg once daily. The maximum daily dose is 25 mg. When used with sulphonylurea or insulin a lower dose of these may be considered to reduce the risk of hypoglycaemia. Renal impairment: The glycaemic efficacy is dependent on renal function. No dose adjustment is required for patients with an eGFR ≥60 ml/min/1.73m2 or CrCl ≥60 ml/min. Do not initiate in patients with an eGFR <60 ml/min/1.73m2 or CrCl <60 ml/min. In patients tolerating empagliflozin whose eGFR falls persistently below 60 ml/min/1.73m2 or CrCl below 60 ml/min, the dose of empagliflozin should be adjusted to or maintained at 10 mg once daily. Discontinue when eGFR is persistently below 45 ml/min/1.73m2 or CrCl persistently below 45 ml/min. Not for use in patients with end stage renal disease (ESRD) or on dialysis. Hepatic impairment: No dose adjustment is required for patients with hepatic impairment. Not recommended in severe hepatic impairment. Elderly patients: No dose adjustment is recommended based on age. In patients 75 years and older, an increased risk for volume depletion should be taken into account. Not recommended in patients 85 years or older. Paediatric population: No data are available. Method of administration: The tablets can be taken with or without food, swallowed whole with water. If a dose is missed, it should be taken as soon as the patient remembers. A double dose should not be taken on the same day. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Warnings and Precautions: Not to be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis (DKA). Rare cases of DKA, including life-threatening and fatal cases, have been reported in patients treated with SGLT2 inhibitors, including empagliflozin. Consider the risk of DKA in the event of non-specific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness and assess patients for ketoacidosis immediately, regardless of blood glucose level. Interrupt treatment for patients hospitalised for major surgical procedures or acute serious medical illnesses. In patients where DKA is suspected or diagnosed, treatment should be discontinued immediately. Before initiating empagliflozin, consider factors in the patient history that may predispose to ketoacidosis. Use with caution in patients who may be at higher risk of DKA. Renal impairment and elderly patients: See under Dose and Administration; special attention should be given to volume intake of elderly patients in case of co-administered medicinal products which may lead to volume depletion (e.g. diuretics, ACE-inhibitors). Monitor renal function prior to initiation and at least annually. Cases of hepatic injury have been reported with empagliflozin in clinical trials. A causal relationship between empagliflozin and hepatic injury has not been established. Haematocrit increase was observed with empagliflozin treatment. Osmotic diuresis accompanying therapeutic glucosuria may lead to a modest decrease in blood pressure. Therefore, caution should be exercised in patients with known cardiovascular disease, patients on anti‑hypertensive therapy with a history of hypotension or patients aged 75 years and older. In case of conditions that may lead to fluid loss (e.g. gastrointestinal illness), careful monitoring of volume status and electrolytes is recommended. Temporary interruption of treatment with empagliflozin should be considered until the fluid loss is corrected. Temporary interruption of empagliflozin should be considered in patients with complicated urinary tract infections. An increase in cases of lower limb amputation (primarily of the toe) has been observed in ongoing long-term clinical studies with another SGLT2 inhibitor, counsel patients on routine preventative footcare. Experience in New York Heart Association (NYHA) class I-II is limited, and there is no experience in clinical studies with empagliflozin in NYHA class III-IV. Due to its mechanism of action, patients taking Jardiance will test positive for glucose in their urine.The tablets contain lactose and should not be used in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose‑galactose malabsorption. Interactions: Use with diuretics may increase the risk of dehydration and hypotension. Insulin and insulin secretagogues may increase the risk of hypoglycaemia therefore, a lower dose of insulin or an insulin secretagogue may be required. The effect of UGT induction on empagliflozin has not been studied. Co-medication with known inducers of UGT enzymes should be avoided due to a potential risk of decreased efficacy. Interaction studies suggest that the pharmacokinetics of empagliflozin were not influenced by coadministration with metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, ramipril, simvastatin, torasemide and hydrochlorothiazide. Interaction studies conducted in healthy volunteers suggest that empagliflozin had no clinically relevant effect on the pharmacokinetics of metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, simvastatin, warfarin, ramipril, digoxin, diuretics and oral contraceptives. Fertility There are no data from the use of empagliflozin in pregnant women. As a precautionary measure, it is preferable to avoid the use of Jardiance during pregnancy. No data in humans are available on excretion of empagliflozin into milk. Jardiance should not be used during breast‑feeding. No studies on the effect on human fertility have been conducted for Jardiance. Undesirable effects: Frequencies are defined as very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), not known (cannot be estimated from the available data). Very common: Hypoglycaemia (when used with sulphonylurea or insulin). Common: Vaginal moniliasis, vulvovaginitis, balanitis and other genital infections, urinary tract infection (including pyelonephritis and urosepsis), thirst, pruritus (generalised), rash, increased urination, serum lipids increased. Uncommon: Urticaria, volume depletion, dysuria, blood creatinine increased/glomerular filtration rate decreased, haematocrit increased. Rare: DKA. Not known: Angioedema. Prescribers should consult the Summary of Product Characteristics for further information on side effects. Pack sizes and NHS price: 10 mg; 28 tablets £36.59, 25 mg: 28 tablets £36.59. Legal category: POM. MA numbers: 10 mg/28 tablets EU/1/14/930/013; 25 mg/28 tablets EU/1/14/930/004. Marketing Authorisation Holder: Boehringer Ingelheim International GmbH, D-55216 Ingelheim am Rhein, Germany. Prescribers should consult the Summary of Product Characteristics for full prescribing information. Prepared in January 2018.

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard

Adverse events should also be reported to Boehringer Ingelheim Drug Safety on 0800 328 1627 (freephone).