Article Type : Short commentary
Authors : Bando H
Keywords : Standards of Medical Care in Diabetes-2022; American Diabetes Association (ADA); Atherosclerotic cardiovascular disease (ASCVD); Chronic kidney disease (CKD); Glucagon-like peptide 1 receptor agonists (GLP-1RAs); Sodium–glucose cotransporter 2 inhibitors (SGLT2i)
American Diabetes Association (ADA) presents “the Standards of Medical Care in Diabetes-2022” on Jan 1, 2022. Metformin has been for long years strongly recommended as a first-line agent for type 2 diabetes mellitus (T2DM). In latest edition, metformin becomes not necessarily first-line, for atherosclerotic cardiovascular disease (ASCVD), heart failure or chronic kidney disease (CKD). For initial combination therapy, glucagon-like peptide 1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) can be applied. If eGFR is 25 mL/min/1.73m2 < or urinary albumin is 300 mg/gCr <, SGLT2i is required to prevent CKD progression and to suppress cardiovascular risk.
American Diabetes
Association (ADA) presents “the Standards of Medical Care in Diabetes-2022” on
Jan 1, 2022 [1]. The official comments were announced on the internet site in
late December, 2021. This significant document has been positioned as a standard
clinical practice guideline for diabetes in the United States (US) and revised
annually for incorporating several new evidence.
When observing the
current situation concerning diabetes, the prevalence of diabetes mellitus (DM)
has been increased across the world for long period [2]. International Diabetes
Federation (IDF) has contributed medical progress of diabetes and estimated
that about one in two adult from 20 to 79 years population with diabetes are
unaware of having diabetes status [3]. Then, adequate management for diabetes
was recommended according to the previous standard guideline from several
points of view [4].
For current ADA
guideline-2022, some characteristic comments were found concerning the
pharmacological treatment recommendation. One of the most popular oral
hypoglycemic agents (OHAs) is metformin. It is finally stepped down from the
only first-line medicine for T2DM [5]. Its reason includes the presence of the
complication of atherosclerotic cardiovascular disease (ASCVD). Until the guideline-2021,
metformin has been strongly recommended as a first-line agent for T2DM as long
as it is not contraindicated and tolerated [6]. On the other hand, latest 2022
edition states that i) first-line treatments basically include metformin and
comprehensive lifestyle-related improvements, ii) it is changed to the
recommendation of judgement for the situation due to actual diabetic
complications, patient-centered medical factors, and current therapeutics [5].
What kind of medical
situation can be found in the case that metformin is not the first-line agent?
There are several recommended medical states when the patient has diabetic
complications, such as present history of ASCVD, high-risk condition, heart
failure or chronic kidney disease (CKD). In this regard, other medications can
be appropriate for initial treatment for T2DM including glucagon-like peptide 1
receptor agonists (GLP-1RAs) and sodium–glucose cotransporter 2 inhibitors
(SGLT2i), which are with/without metformin based on glycemic needs. This
comment was estimated as level A evidence.
When the differences of
ADA guidelines for 2021 and 2022 are investigated, some chapters were actually
changed. Edition in 2021 revealed a chapter including diabetic microangiopathy
and foot care. In contrast, 2022 edition summarized for different chapters of
"CKD and risk management" and "retinopathy, neuropathy, foot
care". This indicates more important clinical significance of CKD and/or
diabetic kidney disease (DKD) in recent diabetic practice and research. Latest
guideline edition has introduction, 1-17 chapters and others [7]. Among them, 9th,
10th and 11th chapters have described Pharmacologic
Approaches to Glycemic Treatment, Cardiovascular Disease and Risk Management,
and Chronic Kidney Disease and Risk Management, respectively.
Recommended difference
was observed for specific agent selection algorithms between 2021 and 2022. In
2021, metformin is the preferred initial pharmacologic agent for T2DM. In 2022,
first-line therapy depends on some comorbidities. They include patient-centered
factors, required management, metformin administration and comprehensive
lifestyle modification [5]. In 9th chapter for pharmacologic
approaches, impressive description is found. For beneficial clinical efficacy
of metformin, Food and Drug Administration (FDA) in US revised the label for
metformin to reflect its safety in patients who has their eGFR > 30
mL/min/1.73m2 [8]. From a randomized trial report, metformin use may bring
vitamin B12 deficiency and exacerbation of neuropathy [9]. For
combination therapy of metformin, longer durability was found for glycemic
efficacy [10]. According to VERIFY (Vildagliptin Efficacy in combination with
metformin for early treatment of type 2 diabetes) trial, initial combination
treatment showed superiority to sequential medication addition for extending
primary/secondary failure [11].
In recent practice for
diabetes, some new class of non-insulin agents are observed. They include
GLP-1RAs, SGLT2i, and dipeptidyl peptidase-4 inhibitors (DPP-4i). From
meta-analysis for comparative effectiveness, these agents in addition to
metformin as initial therapy could generally decrease HbA1c value about 0.7 to
1.0% successfully [12]. In addition to metformin-based background treatment, a
systemic review and network meta-analysis research was conducted. As a result,
greatest HbA1c decreases were observed with specific GLP-1RAs and insulin
regimens [13]. There is recent
remarkable pharmacologic progress concerning GLP-1 RA. As most GLP-1 RAs have
been provided by injection, oral administration became possible in the case of
semaglutide [14]. It is already commercially available with evidence of
clinical efficacy by a series of PIONEER studies [15,16].
In order to obtain the
reduction in risk of diabetes-related complications, comprehensive approach
method is indispensable [17]. It is like constructing a robust building. As a
concrete foundation plate, lifestyle modification and diabetes education are
set in the ground. As a framework of four steel frames,?4 pillars of glycemic management, blood pressure
management, lipid management and agents with cardiovascular and kidney benefit
are set upright. After that, broad roof can be put on 4 pillars, which
indicates the reduction in diabetes complications. From these construction and
maintenance, global risk reduction in diabetes will be expected [18].
As regards to CKD or DKD,
some changes in recommendation were observed [19]. In the previous edition,
considering SGLT2i was recommended for eGFR 30 mL/min/1.73 m2 or higher and
urinary albumin 300 mg/gCr or higher for T2DM with DKD. In contrast, latest
edition describes as follow: if eGFR is 25 mL/min/1.73m2 or more and urinary
albumin is 300 mg/gCr or more, SGLT2i is required to prevent CKD progression
and to suppress cardiovascular risk. Furthermore, a novel mineral corticoid
receptor antagonist (MRA) as finerenone was described [20]. It can be given to
the patients with high cardiovascular risk or risk of CKD progression who
cannot tolerate SGLT2i, associated with the evidence level A [21].
In summary, latest
information and news concerning ADA guideline-2022 was introduced. This article
becomes hopefully a useful reference for diabetic practice.
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