medwireNews: An algorithm based on real-world clinical data could support decisions between use of sodium-glucose cotransporter (SGLT)2 inhibitors and dipeptidyl peptidase (DPP)-4 inhibitors in people with type 2 diabetes.
The research team led by John Dennis (Royal Devon and Exeter Hospital, UK) aimed to identify subgroups of people who would achieve markedly larger reductions in glycated hemoglobin (HbA1c) with one medication class versus the other during the first 6 months of use.
“Combining just five routinely measured clinical features into a treatment selection algorithm can identify a large patient subgroup (around four in ten of UK patients) with a predicted glycaemic benefit of 5 mmol/mol or greater on SGLT2 inhibitors compared with DPP-4 inhibitors, and a similar risk of early discontinuation for both agents,” say the researchers.
They add: “Only one in seven of this group would be preferentially recommended SGLT2 inhibitors based on current guidelines.”
These people were predominantly male (66.6%), and relative to the rest of the study cohort they had a young median age of 55 years, and high median baseline BMI (34.1 kg/m2), HbA1c (80 mmol/mol; 9.5%), estimated glomerular filtration rate (eGFR; 97 mL/min per 1.73 m2), and alanine transaminase (37 IU/L).
The five predictive features, in order of highest to lowest amount of variation in treatment response they explained, were baseline HbA1c, eGFR, alanine transaminase, and BMI, followed by current age. Together these explained 29% of the variation in on-treatment HbA1c change.
And there was a smaller subgroup, of about 5% of people, predicted to achieve at least a 3 mmol/mol greater HbA1c reduction if given a DPP-4 inhibitor rather than an SGLT2 inhibitor. These people were relatively older (median 79 years), compared with the overall cohort, with lower median BMI (26.5 kg/m2), HbA1c (61 mmol/mol; 7.7%), eGFR (59 mL/min per 1.73 m2), and alanine transaminase (15 IU/L).
Of note, people in this subgroup were also significantly less likely to discontinue DPP-4 inhibitors than SGLT2 inhibitors, at rates of 14.9% versus 33.1%.
“However, due to older age and more severe cardiorenal disease profile, most of this group would be preferentially recommended SGLT2 inhibitors based on current guidelines,” write the study authors in The Lancet Digital Health.
The researchers drew on data from 10,253 people initiating an SGLT2 inhibitor and 16,624 starting a DPP-4 inhibitor as a non-first-line treatment, identified in the UK Clinical Practice Research Datalink from 2013 to 2019. These were divided into a derivation and validation cohort, and the findings were additionally verified using data from 10,414 participants of 14 clinical trials of SGLT2 and DPP-4 inhibitors.
“Although not all associations for individual clinical features observed in routine clinical data were replicated in the trials, specifically associations between higher age and lower eGFR with a greater DPP-4 inhibitor response, the algorithm performed well in validation,” the researchers note.
They stress that the algorithm’s predictions “are not intended to be prescriptive,” but rather to support informed discussions between clinicians and people with diabetes.
In a linked commentary, Oriana Hoi Yun Yu (Jewish General Hospital, Montreal, Quebec, Canada) and Ju-Young Shin (Sungkyunkwan University, Suwon, South Korea) highlight other critical factors such as medication costs and the criteria for reimbursement.
And they also note the need to validate the findings in different patient populations, with different medications, over longer treatment periods, and to explore subgroups such as people with a healthy BMI, for whom there is currently “insufficient evidence to provide recommendations for disease management.”
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Lancet Digit Health 2022; 4: e873–883
Lancet Digit Health 2022; 4: e851–852