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driven by the advent of novel medication classes such as sodium-glucose co-transporter inhibitors (SGLT2s)
and Glucagon-Like Peptides receptor agonists (GLP-1s); recent data and guidelines have even questioned
the glucocentric nature of diabetes management. While the current treatment options provide many
considerations for the person with type 2 diabetes, it does pose questions as to where do the existing
therapies sit. Additionally, as data continue to arrive, the increasing burden of multimorbidity in those with
type 2 diabetes and new molecules being developed, one must consider the impact and future landscape of
type 2 diabetes care.

This article will highlight the recent advances in the pharmacological management of type 2 diabetes,
current perspectives, future considerations of comorbidities, and therapeutic options. It will largely focus on
non-insulin therapies except in certain settings.

CURRENT LANDSCAPE
Up until relatively recently, type 2 diabetes management centered around Hba1c lowering and
cardiovascular risk factor management. Recent cardiovascular outcome trials, as mandated by the Food and
Drug Administration, resulted in evidence of superiority in some medications within the SGLT2 and GLP-1
[1]
RA classes for cardiovascular outcomes . Additionally, benefits in heart failure hospitalization reduction
and renal outcomes (in the setting of SGLT2s) have resulted in a shift in guidelines from being glucose-
centered (glucocentric) to highlighting cardiovascular disease and CV risk assessment at the onset of any
management considerations. One of the first diabetes-specific guidelines to focus on this was the joint
American Diabetes Association and the European Association for the Study of Diabetes (ADA-EASD)
guidelines which incorporated cardiovascular risk assessment as part of the initial management (following
[2]
metformin, dietary and lifestyle advice) . However, even these guidelines appear to have now progressed,
with the most recent draft guidelines (2022) highlighting CV risk assessment independent of glucose
[3]
lowering .

The low Numbers Needed To Treat (NNT) of SGLT2 inhibitors and the multitude of beneficial effects were
so apparent that the National Institute for Clinical Excellence (NICE), long known to champion the balance
between cost-effectiveness and clinical effectiveness, has now also included SGLT2s as a first-line therapy
irrespective of Hba1c level in those with established ASCVD or heart failure or high cardiovascular risk .
[4,5]
While these guidelines highlight the use of SGLT2s, they fall short of recommending dual initiation directly
but suggest separate consideration. As the development of SGLT2s and incretins continues, the role of
traditional medications remains under debate. While data from UKPDS and multiple metanalyses show that
metformin remains a key agent in the treatment of type 2 diabetes, its role in the modern management of
cardiovascular disease specifically is starting to diminish compared to the stronger evidence base for
[6]
SGLT2s and GLP-1s in this area . However, its role in a pure glucocentric sense remains in most, if not all,
guidelines.

With the move towards these newer therapies, one might question the role of the other ‘traditional’
medications in the modern and future management of Type 2 Diabetes Mellitus. This will be discussed in
more detail in the article with reference to more recent trials of medications as seen in[Table 1].

ROLE OF SULPHONYLUREAS, THIAZOLIDINEDIONES, AND DIPEPTIDYL PEPTIDASE-4
INHIBITORS
Sulphonylureas are moving further out of favour in many places due to the rise of medications with
extraglycaemic benefits and lesser side effect profiles, specifically lower hypoglycaemia risk and weight
neutrality or reduction. The risk of hypoglycaemia in diabetes is well known and the impact on