Dr Sharon Rees @reesprescribe
Day 1: In the 1990s, growing insight into incretin roles in type 2 (T2DM) diabetes led to an interest in the breakdown of gut hormone GLP-1. DPP-4 was identified as the best peptidase target and a piperazine derivative #sitagliptin was found to be a potent and selective inhibitor; licensed in 2006–2007.
Dr Sharon Rees @reesprescribe
Day 2: An oral hypoglycaemic, #sitagliptin was the first DPP-4 inhibitor in class (there are now 5 ‘gliptins’). Not first line, but can be used in adults as monotherapy (with diet/exercise), or as an add-on at various levels of T2DM treatment (including with insulin). With a dose of 100 mg and administered once daily, it also comes as a tablet combination with metformin. It should be noted that a lower dose may be needed if used with other hypoglycaemic agents, such as insulin.
Dr Sharon Rees @reesprescribe
Day 3: Rapid oral absorption (food has no effect) with high bioavailability and Vd. Low plasma protein binding. Minor hepatic CYP3A4 metabolism, but majority renally excreted unchanged (minor in faeces). Dose adjustment if eGFR <45 mL/min, but no dose change for hepatic function, or elderly.
Dr Sharon Rees @reesprescribe
Day 4: By inhibiting the breakdown of gut incretins eg GLP-1, #sitagliptin augments incretin function; this increases insulin output and reduces glucagon release. This leads to improved glucose homeostasis (not linked to body weight changes). Average HbA1c reduction 0.5–0.9% (upper range in combination with other hypoglycaemic agents).
Dr Sharon Rees @reesprescribe
Day 5: Common ADEs for #sitagliptin include: headache and hypoglycaemia (with other anti-diabetic drug use, as #sitagliptin response is glucose-dependent). Uncommon/serious include constipation, skin reactions, Stevens-Johnson syndrome, renal impairment and acute pancreatitis. The frequency of joint pain and myalgia is unknown.
Dr Sharon Rees @reesprescribe
Day 6: There are no ‘severe’ drug–drug interactions for #sitagliptin. As previously noted, a combination with other diabetic drugs can lower blood glucose and cause hypoglycaemia. Some interactions eg digoxin and ciclosporin are listed in the SPC, but not the BNF; SPC advises additional monitoring.
Dr Sharon Rees @reesprescribe
Day 7: Severe and disabling joint pain has been reported for DPP-4 inhibitors, which may occur on drug initiation or years later (reversible on stopping). The FDA added a warning in 2015, but the EMA has no special warning. SPC for #sitagliptin has ‘frequency unknown’ for general musculoskeletal ADEs.
Earn Your Cpd Certificate
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In addition to the tweets, read the BNF treatment summary on ‘Type 2 diabetes’ and the monograph for sitagliptin, as well as the Summary of Product Characteristics for sitagliptin. Please submit the answers to reesprescribe@gmail.com as a numbered list with TRUE/FALSE or the correct A,B,C,D option. If you achieve 8 or more out of 10 on the questions, a CPD certificate will be emailed to you.
Further reading on #sitagliptin
- Type 2 diabetes: https://bnf.nice.org.uk/treatment-summaries/type-2-diabetes/
- JANUVIA 100mg film-coated tablets:https://www.medicines.org.uk/emc/product/7887/smpc
- Sitagliptin: https://bnf.nice.org.uk/drugs/sitagliptin/
Answer the following questions
Sitagliptin was the first of 5 DPP-4 inhibitors
TRUE or FALSE?
The DPP-4 inhibitors act on all of the peptidase enzymes in the gut
TRUE or FALSE?
Which of the following is TRUE?
- Sitagliptin is licensed in all age groups
- Sitagliptin comes in many formulations
- Sitagliptin may be used for type 1 and 2 diabetes mellitus
- Sitagliptin is dosed once daily unless in a combined tablet with metformin
Sitagliptin can be used with all hypoglycaemic medicines apart from insulin
TRUE or FALSE?
Which of the following is TRUE?
- Increasing gut incretin activity by DPP-4 inhibition leads to lower glucose levels
- Reducing gut incretin activity by DPP-4 agonism leads to lower glucose levels
- Increasing DPP-4 enzyme activity stimulates insulin output
- Increasing DPP-4 enzyme activity stimulates glucagon output
Sitagliptin is associated with weight loss in type 2 diabetes
TRUE or FALSE?
Sitagliptin is considered a hypoglycaemic with a strong effect on reducing HbA1c levels when used alone
TRUE or FALSE?
The ‘gliptins’ are not themselves associated with hypoglycaemia
TRUE or FALSE?
There are multiple severe drug-drug interactions for sitagliptin
TRUE or FALSE?
There have been warnings about severe joint pain for all the ‘gliptin’ drugs
TRUE or FALSE?