GLP-1 RA & dual GIP/GLP-1 RA (Formulary: Endocrine)

TAM (Treatments and Medicines) NHS Highland
NHS Highland

Definitions:

  • GLP-1 RA: glucagon-like peptide-1 receptor agonist
  • GIP/GLP-1 RA: Dual glucose-dependent insulinotropic polypeptide / GLP-1 RA

Note re medicines for weight management

Currently GLP-1 RAs & dual GIP/GLP-1 RAs are NOT recommended to be prescribed in NHS Highland for weight management.

MHRA advice:

  • GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists: strengthened warnings on acute pancreatitis, including necrotising and fatal cases (January 2025) (www.gov.uk).
  • GLP-1 and dual GIP/GLP-1 receptor agonists: potential risk of pulmonary aspiration during general anaesthesia or deep sedation (January 2025) (www.gov.uk).
  • GLP-1 receptor agonists: reminder of the potential side effects and to be aware of the potential for misuse (October 2024) (www.gov.uk).
  • GLP-1 receptor agonists: reports of diabetic ketoacidosis when concomitant insulin was rapidly reduced or discontinued (June 2019) (www.gov.uk).

Note re women of childbearing potential:

  • Women of childbearing potential ARE RECOMMENDED to use contraception when treated with GLP-1 RAs and dual GIP/GLP-1 RAs.

SEMAGLUTIDE - (First line)

Therapy notes

  • MHRA advice:
    • Semaglutide (Wegovy, Ozempic and Rybelsus): risk of Non-arteritic Anterior Ischemic Optic Neuropathy (NAION) (February 2026) (www.gov.uk).
    • Ozempic (semaglutide) and Saxenda (liraglutide): vigilance required due to potentially harmful falsified products (November 2023) (www.gov.uk).
Women of childbearing potential are recommended to use contraception when treated with semaglutide/liraglutide/dulaglutide/tirzepatide.

Place in therapy: FIRST LINE due to increase in clinical effectiveness

Guidelines:

Formulation and dosage details

Formulation:

Solution for injection, pre-filled pen (Ozempic) 0·25mg, 0·5mg and 1mg (Restriction: can be initiated by clinicians who are experienced in the treatment of diabetes, for other circumstances: specialist recommendation only.)

Dosage:

As per SMC 2092: : the treatment of adults with insufficiently controlled type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise:

  • As monotherapy when metformin is considered inappropriate due to intolerance or contraindications
  • In addition to other medicinal products for the treatment of diabetes.

SMC restriction: In addition to other oral anti-diabetic medicines, or as an add-on to basal insulin, as an alternative glucagon-like peptide-1 receptor agonist option. 

Note: Maximum recommended dose is 1mg. While the maximum licensed dose is 2mg, the maximum recommended dose for diabetes is 1mg, and this is the highest available dose in the UK.

Formulation and dosage details

Formulation:

Tablets (Rybelsus) 1.5mg, 4mg and 9mg (Restriction: can be initiated by clinicians who are experienced in the treatment of diabetes, for other circumstances: specialist recommendation only.)

  • MHRA advice: Rybelsus® (semaglutide tablets): transition to new formulation and risk of medication error (December 2025) (www.gov.uk).

NOTE: The new formulation of Rybelsus® is replacing the previous formulation in a smaller tablet, that offers equivalent efficacy, safety and administration.

  • The new and previous formulation tablet bioequivalencies are given in the table below. 
Rybelsus
PREVIOUS formulation, oval tablet		 Bioequivalent Rybelsus
NEW formulation, round tablet
3mg (starting dose) ≡ 1.5mg (starting dose)
7mg (maintenance dose) ≡ 4mg (maintenance dose)
14mg (maintenance dose) ≡ 9mg (maintenance dose)

Dosage:

As per SMC2287: for the treatment of adults with insufficiently controlled type 2 diabetes mellitus to improve glycaemic control as an adjunct to diet and exercise:

  • As monotherapy when metformin is considered inappropriate due to intolerance or contraindications
  • In combination with other medicinal products for the treatment of diabetes.

SMC restriction: In addition to other oral anti-diabetic medicines, or as an add-on to basal insulin, as an alternative glucagon-like peptide-1 receptor agonist option.

Further information 

DULAGLUTIDE - (Second line)

Therapy notes

Place in therapy: Second line once weekly option.

  • Needle is hidden which may be suitable for those with a needle phobia. 

Formulation and dosage details

Formulation:

Injection, pre-filled pen 750 micrograms/0·5mL, 1·5mg/0·5mL (Restriction: can be initiated by clinicians who are experienced in the treatment of diabetes, for other circumstances: specialist recommendation only.)

Dosage:

  • As per SMC 1110/15: in adults with type 2 diabetes mellitus to improve glycaemic control as
    add-on therapy in combination with other glucose-lowering medicinal products including insulin, when these, together with diet and exercise, do not provide adequate glycaemic control. 
    SMC restriction: as part of a triple therapy in patients with inadequate glycaemic control on two oral anti-diabetic drugs, as an alternative glucagon-like peptide 1 (GLP-1) agonist option.
  • As add on therapy, 1·5mg once weekly, however consider a starting dose of 750 micrograms once weekly for potentially vulnerable populations such as those aged 75 years or over.
    If adding to existing metformin and/or pioglitazone therapy, continue the current dose of metformin/pioglitazone.

Guidelines

TIRZEPATIDE - (Third line)

Therapy notes

Caution. For full details see BNF and Manufacturer information

  • Tirzepatide delays gastric emptying, particularly following the first dose.  This has the potential to slow the rate of absorption of concomitant oral medicines.  The risk of a delayed effect should be considered for oral medicines where a rapid onset of action is important.  Monitor patients on oral medicines with a narrow therapeutic index, especially at the start of tirzepatide treatment and after dose increases.
  • Since reduced efficacy of oral contraceptives cannot be excluded, it is advised that female patients who are overweight or obese and using an oral contraceptive should add a barrier method of contraception or switch to a non-oral contraceptive method for the first 4 weeks of treatment, and for 4 weeks after each dose increase.
  • Discontinue treatment at least one month before planned pregnancy.

Place in therapy: Third line, less cost-effective option. 

  • Generally after a trial of GLP-1 receptor agonist (RA). This guidance is based on the lack of confirmed CV benefit at present.
  • As an alternative to GLP-1 RAs in the following instances:
    • Supply issue with existing GLP-RAs
    • Suboptimal glycaemia despite GLP-1 RA use
    • High risk individuals in where greater weight loss will have a positive benefit on obesity related complications e.g. young onset, Obstructive Sleep Apnoea etc.

Formulation and dosage details

Formulation:

KwikPen 2.5mg, 5mg, 7.5mg, 10mg, 12.5mg, 15mg solution for injection in prefilled pen (Restricted: Specialist recommendation only)

Dosage:

As per SMC2633: for the treatment of adults with insufficiently controlled type 2 diabetes mellitus as an adjunct to diet and exercise and in addition to other oral anti-diabetic medicines as an option when glucagon-like peptide-1 (GLP-1) receptor agonists would be considered.

Adult: Initially 2.5 mg once weekly for 4 weeks, then increased to 5 mg once weekly for at least 4 weeks, then increased if necessary up to 15 mg once weekly, dose to be increased in steps of 2.5 mg at intervals of at least 4 weeks.

Guidelines

Editorial Information

Last reviewed: 26/06/2025

Version: 2.2

Approved By: TAM Subgroup

Document Id: F175