ONE YEAR ON: GPS PRAISE NICE GUIDELINE UPDATE ON TYPE 2 DIABETES NEWER AGENTS

Over half of GPs have changed prescribing habits as a result¹

23 June 2010 ? A new survey of GPs shows that the National Institute for Health and Clinical Excellence (NICE) guideline on the use of newer agents for blood glucose control in type 2 diabetes patients is being endorsed by GPs,¹ as shown by prescribing habits just one year on from the launch of the recommendations.¹ Confidence amongst primary care for the NICE recommendations is clearly visible, with two thirds (67 percent) of those surveyed seeing the guideline as positive,¹ evidenced by an uplift in prescribing newer therapies.¹

Fifty-nine percent of GPs claim their prescribing of the DPP-4 inhibitor class, which includes sitagliptin, has increased over the last year¹ based on the advice and 44 percent of the group felt their prescribing of GLP-1 analogues has increased.¹ Inversely, 40 percent claimed that their prescribing of the older treatments decreased, specifically sulphonylureas (SUs)¹ and thiazolidinediones (TZDs),¹ which are often associated with concerns around hypoglycaemia² risk and weight gain³ respectively. Metformin is widely used as first line oral therapy⁴ and remains a mainstay of diabetes therapy.

When asked what the main benefits of newer treatments were, 83 percent of GPs taking part in the survey selected blood glucose control.¹ In addition, a low risk of weight gain and of hypoglycaemia, were recognised as benefits by 70 percent of the same GP group.¹

“It is very encouraging to see that the introduction of the NICE guideline has supported a change in the way type 2 diabetes patients are treated in the UK,” said Eugene Hughes a GP specialist in diabetes, from the Isle of Wight. “Good blood glucose control, achieved early in the disease process, has the potential to reduce the microvascular and macrovascular complications of diabetes.”

Of interest, the survey shows that nearly half (44 percent) of GPs believe the main concerns raised by patients in consultations about type 2 diabetes is concern about injections,¹ despite availability of oral therapies,⁴ and 58 percent raise concerns about the impact of type 2 diabetes on their long term health.¹ Dr Hughes added, “Oral treatments, such as the DPP-4 inhibitors, may help doctors to overcome patient concerns, encouraging their adherence to therapy. The move to use new treatment options second line, particularly the DPP-4 inhibitor class, is most likely related to the patient benefits, specifically achieving good reductions in blood glucose but with a low risk of hypoglycaemia and of weight gain.” The survey highlights that weight gain is the main concern raised by type 2 diabetes patients with their GPs (74 percent).

GPs signalled that this change in the treatment paradigm for type 2 diabetes patients is likely to continue.¹ Whilst 59 percent of GPs claim to be already prescribing DPP-4 inhibitors,¹ a further 25 percent claim they plan to prescribe DPP-4 inhibitors in the future.¹

NICE guideline

Of the new treatment options, the NICE guideline recommends that the DPP-4 inhibitor class, including sitagliptin (‘Januvia’), should be considered as a second-line therapy instead of a sulphonylurea (SU) when blood glucose control remains or becomes inadequate (HbA1c ≥ 6.5% or other higher level agreed with the individual) with metformin in patients at significant risk of hypoglycaemia or its consequences, or if a person does not tolerate SUs or SUs are contraindicated.⁴  It recognises sitagliptin as the only DPP-4 inhibitor licensed for use in triple therapy with metformin and an SU, where metformin and an SU do not adequately control blood sugar (HbA1c ≥7.5% or higher level agreed with the individual) and insulin is considered inappropriate or unacceptable to the patient.⁴ As a once-daily tablet, sitagliptin provides a convenient treatment option for patients, with over twenty one million prescriptions issued worldwide since launch.⁵

Earlier this month, ‘Janumet’ the combination of mainstay metformin and newer therapy sitagliptin in one tablet launched in the UK.⁶ The SMC have already granted its approval in Scotland.⁷

 

References

1.     Data on file.  HCP survey run by Kantar Health on behalf of MSD.

2.     Amiel SA, Dixon T, Mann R et al. Hypoglycaemia and Type 2 Diabetes. Diabetic Medicine. March 2008; 25(3): 245?254

3.     Hermansen, Kjeld; Morensen, Lene S. Bodyweight changes associated with antihyperlycaemic agents in type 2 diabetes mellitus. Drug Safety: 2007 ? Vol. 30, Issue 12, pp 1127-1142

4.     National Institute for health and Clinical Excellence. Type 2 diabetes: newer agents for blood glucose in type 2 diabetes. Review of NICE technology appraisal guidance 66. May 2009. www.nice.org.uk

5.     MSD: data on file.

6.     ‘Janumet’ (sitagliptin/metformin). Summary of Product Characteristics. March 2010

7.     SMC Product Update. ‘Janumet’. Issued 9 April 2010

8.     ‘Januvia’ (sitagliptin). Summary of Product Characteristics. November 2009.

9.     Diabetes UK. Diabetes Information on hypoglycaemia. https://www.diabetes.org.uk/Documents/catalogue/Hypoglycaemia%20new.pdf (Last checked June 2010)

10.   National Institute for health and Clinical Excellence (NICE). About NICE. http://www.nice.org.uk/aboutnice/ (Last checked June 2010)

 

 

A separate analysis shows patients on sitagliptin are five times more likely to achieve HbA1c reductions with low risk of hypoglycaemia and weight gain compared to glipizide -

London, 28 June, 2010 ? Type 2 diabetes patients who begin initial therapy on MSD's ‘Janumet’ (sitagliptin/metformin) have significantly improved glycaemic control over 32 weeks compared to patients taking pioglitazone,¹ according to results from a study presented today at the American Diabetes Association (ADA) 70^th Annual Scientific Sessions in Orlando, USA. In addition, patients taking sitagliptin/metformin also experienced weight loss while patients taking pioglitazone experienced weight gain.¹ Sitagliptin/metformin was launched as a single tablet in the UK last month. ² 'Janumet' is not licensed for initial therapy in the UK*.²

A mean reduction in HbA1c of 1.9 percent from baseline was seen in patients taking sitagliptin/metformin, compared with 1.4 percent for patients taking pioglitazone a significant between-group difference of 0.5 percent (p<0.001).¹ Significantly more patients taking sitagliptin/metformin as initial therapy achieved the American Diabetes Association HbA1c goal of less than 7.0 percent, compared with patients taking pioglitazone (57 percent vs. 43 percent, respectively; p<0.001).¹ These improvements in glycaemic control were accompanied by a weight loss of 1.4 kg in patients taking sitagliptin/metformin, while patients taking pioglitazone experienced a weight gain of 3.0 kg, a significant between-group difference of 4.5 kg or approximately 10 lbs (p<0.001).¹

Achieving a reduction in HbA1c without weight gain is important for patients, as a recent survey of UK GPs found that 74 percent cite weight gain as one of the main concerns raised by type 2 diabetes patients they see,³ with 32 percent ranking weight gain as the number one concern.³

 “When choosing a treatment it is important to strike the balance between effective therapy and tolerability/side effects.  This study shows that newer treatments, such as sitagliptin or the combination of sitagliptin/metformin, may provide advantages over some of the more traditional treatments, particularly a lower risk of weight gain.” commented Professor Anthony Barnett, Heart of England NHS Foundation Trust, Birmingham, UK.

A separate post hoc analysis with sulphonylurea (SU) glipizide was also presented at the ADA, looking at composite endpoint defined as a reduction in HbA1c of greater than 0.5 percent, no hypoglycaemia and no weight gain.⁴ Patients receiving sitagliptin were shown to be five times more likely to achieve this composite endpoint than patients treated with glipizide (5.43 [95 percent CI: 3.70, 7.96]).⁴

This builds on results from the original study which showed that patients on the SU glipizide, experienced more than 10 times as many hypoglycaemic events compared to those patients on sitagliptin.⁴ Furthermore, patients on sitagliptin experienced a weight reduction, compared to an increase in weight for patients on glipizide (-1.5 kg vs. + 1.1 kg respectively, a significant difference of 2.5 kg [-3.1, -2.0; p<0.001] or 5.5 pounds).⁴

 “Sulphonylureas are commonly associated with an increased risk of hypoglycaemic events. Hypoglycaemia can be dangerous and certainly reduce quality of life and patient adherence to treatment.⁵ The availability of newer treatment options to help reduce this risk is valuable and may potentially help patients to better manage their condition,” added Professor Anthony Barnett.

About sitagliptin/metformin

‘Sitagliptin/metformin’ licence includes:

・       As an adjunct to diet and exercise to replace sitagliptin and metformin in patients with type 2 diabetes already being treated with metformin and sitagliptin or to replace metformin in patients inadequately controlled on the maximal tolerated dose of metformin, metformin and a sulphonylurea or metformin and a glitazone²

・       As an add-on to insulin when a stable dosage of insulin and metformin plus diet and exercise does not provide adequate control²

The dose of antihyperglycaemic therapy with fixed dose combination of sitagliptin and metformin should be individualised on the basis of the patient’s current regimen, effectiveness, and tolerability while not exceeding the maximum recommended daily dose of 100mg sitagliptin.²

Please note, initial therapy with sitagliptin/metformin combination is not currently licensed in the UK.

The fixed dose combination of sitagliptin and metformin is contraindicated in patients with: hypersensitivity to the active substances or to any of the excipients; diabetic ketoacidosis or diabetic pre-coma; moderate and severe renal impairment or abnormal creatinine clearance, acute conditions with the potential to alter renal function; acute or chronic disease which may cause tissue hypoxia; hepatic impairment; acute alcohol intoxication; alcoholism and lactation. This drug combination should not be used in patients with type 1 diabetes.²

Patients taking the fixed dose combination of sitagliptin and metformin with a sulfonylurea, a medication known to cause hypoglycaemia, may be at a higher risk of hypoglycaemia than those patients taking sitagliptin/metformin fixed dose combination alone. Therefore, a reduction in the dose of the sulfonylurea may be required.²

In clinical studies, the most common adverse reactions reported, regardless of investigator assessment of causality, in ≥5% of patients and more commonly than in patients treated with placebo were as follows: diarrhea, upper respiratory tract infection, and headache (for initial sitagliptin and metformin combination therapy); nasopharyngitis (for sitagliptin monotherapy); and diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache (for metformin therapy).²

SMC has approved ‘Sitagliptin/metformin’ for restricted use within NHS Scotland as an adjunct to diet and exercise to improve glycaemic control in patients with type 2 diabetes mellitus inadequately controlled on their maximal tolerated dose of metformin alone, or those already being treated with the combination of sitagliptin and metformin.⁶

 

About sitagliptin

Sitagliptin is a member of a class of oral anti-hyperglycaemic agents called dipeptidyl peptidase 4 (DPP-4) inhibitors. The drug enhances the body’s own ability to lower blood sugar levels by increasing the levels of the body’s own active incretins, called GLP-1 and GIP.⁷

The recommended dose of sitagliptin is 100mg once daily, with or without food, for all approved indications.⁷

Clinical experience with sitagliptin in patients with moderate to severe renal insufficiency is limited.  Therefore sitagliptin is not recommended in this patient population.  No dosage adjustment is needed for patients with mild to moderate hepatic insufficiency and sitagliptin has not been studied in patients with severe hepatic insufficiency.  Sitagliptin is contraindicated in patients with hypersensitivity to the active substances or to any of the excipients. This medicine should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis, or in woman who are lactating or pregnant.⁷

In studies of sitagliptin 100 mg alone compared to placebo, adverse reactions considered as drug-related reported in patients treated with sitagliptin in excess (> 0.2 % and difference > 1 patient) of that in patients receiving placebo are headache, hypoglycaemia, constipation, and dizziness.⁷

Post-marketing experience additional side effects have been reported (frequency not known): hypersensitivity reactions, including anaphylaxis, angioedema, rash urticaria cutaneous vasculitis and exfoliative skin conditions including Stevens-Johnson syndrome; pancreatitis.⁷

Also, adverse experiences reported regardless of causal relationship to medication and more commonly in patients treated with 'Januvia' included upper respiratory tract infection, nasopharyngitis, osteoarthritis and pain in extremity. ⁷

  References:

1.     Katz, L. et al. Initial Therapy with the Fixed-Dose Combination of Sitagliptin and Metformin Results in Greater Improvement in Glycemic Control Compared with Pioglitazone in Patients with Type 2 Diabetes. Presented at the American Diabetes Association 70th Annual Scientific Sessions, 26^th June 2010. (Poster 546-P)

2.     ‘Janumet’ (sitagliptin/metformin). Summary of Product Characteristics. March 2010

3.     Data on file.  HCP survey run by Kantar Health on behalf of MSD.

4.     Seck, L. et al. Sitagliptin more effectively achieves a composite endpoint for A1C reduction, lack of hypoglycaemia and no body weight gain compared with the sulfonylurea, Glipizide. Presented at the American Diabetes Association 70^th Annual Scientific Sessions, 26^th June 2010. (Poster 024

5.     Amiel SA, Dixon T, Mann R et al. Hypoglycaemia and Type 2 Diabetes. Diabetic Medicine. March 2008; 25(3): 245?254.

6.     SMC Product Update. ‘Janumet’. Issued 9 April 2010

7.     ‘Januvia’ (sitagliptin). Summary of Product Characteristics. November 2009.

(28/6/10)