Individualizing Type 2 Diabetes Management

American Diabetes Association 2022 Standards of Care update.

The American Diabetes Association (ADA) published the annual update to its Standards of Medical Care in Diabetes in January 2022. This article will discuss key changes and updates to the Standards of Care as it pertains to adults with type 2 diabetes. We will provide information on:

• New screening recommendations
• Paradigm shift in management: individualizing care of patients with type 2 diabetes mellitus
• Diabetes technology
• Expansion of care models

New Screening Recommendations

In 2019, the CDC estimated that 37.3 million people of all ages had diabetes. Of those, it is estimated that 8.5 million adults are undiagnosed. This makes up 23 % of all patients with diabetes.

The CDC also estimates that prediabetes has an annual medical cost of $500 per person associated with it. Undiagnosed diabetes can cost $4,250 per person, and diagnosed diabetes costs $13,240 per person.

Diabetes is also the leading cause of end-stage renal disease and new cases of blindness in adults. It is also the seventh leading cause of death as of 2019.

Based on these numbers alone, the economic and health burden has been a driving force to reevaluate our screening processes. The recommended age for screening for all asymptomatic adults has changed to 35 years old, which is younger than the previous recommendations. Testing should be considered in patients over 18 if any of the following apply:

• Overweight/obese
• First-degree relative with diabetes mellitus
• High-risk race/ethnicity (e.g. African American, Latino, Native American, Asian American, Pacific Islander)
• History of cardiovascular disease (CVD)
• Hypertension
• HDL < 35 mg/dl or Triglycerides >250 mg/dl
• Women with polycystic ovarian syndrome
• Physical inactivity
• Other clinical conditions leading to insulin resistance (e.g. acanthosis nigricans)

Paradigm Shift in Management to Individualizing Care

Over the course of the past several years, there has been a paradigm shift in the management of type 2 diabetes mellitus. Clinicians have long held a glucose-centric view with A1c-lowering being the primary consideration. This is because it is well-established that optimization of glycemic control prevents the development of microvascular complications, namely retinopathy, nephropathy and neuropathy. Current guidelines recommend a patient-centric approach, where in addition to A1c lowering, comorbidities and risks must also be considered with an emphasis on individualizing therapy based on these.

Although lifestyle modification and metformin remain the mainstay of management, additional agents should be discussed based on patient comorbidities, namely atherosclerotic cardiovascular disease (established ASCVD/high risk for ASCVD), chronic kidney disease (CKD) and congestive heart failure (CHF). Development of versatile newer agents like the SGLT-2 inhibitors and GLP-1 receptor agonists has been most welcome. These medications have been shown to be effective in lowering both microvascular and macrovascular complications, such as ASCVD, CKD and CHF.

In addition to the labeled indications for prescribing these medications, many advantages should be considered. SGLT-2 inhibitors, despite requiring dosage adjustments in the setting of renal impairment, offer a reduction in albuminuria, and several medications have been shown to slow progression of kidney disease. (See Table 2 for eGFR dosing recommendations.) While not an indication for prescribing independently, this class of medication also provides a reduction in uric acid and weight, which is of significant benefit to many patients.

GLP-1 Receptor Agonists (GLP-1 RA) also provide significant weight loss benefits, as well as risk reduction in patients with ASCVD. In a meta-analysis of trials comparing various classes of medications approved for diabetes, GLP-1 RAs reduced the risk of CV mortality, all-cause mortality and stroke. (Kanie T, Mizuno A, Takaoka Y, et al. Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis. Cochrane Database Syst Rev. 2021;10:CD013650. doi:10.1002/14651858.CD013650.pub2, 10.1002/14651858.CD013650.pub2)

Table: SGLT-2 Inhibitors

Drug Name	Brand Name	Labeled Indications	A1c Reduction	GFR Cutoff Type 2 Diabetes Treatment
Canagliflozin	Invokana	DM, Type 2 ASCVD DKD	100 mg: -0.77% 300 mg: -1.03% With concomitant weight reduction efforts	eGFR ≥60 mL/minute/1.73 m2: No dosage adjustment necessary. eGFR 30 to <60 mL/minute/1.73 m2: 100 mg once daily. eGFR <30 mL/minute/1.73 m2 not recommend
Dapagliflozin	Farxiga	DM, Type 2 CKD HFrEF HFpEF	Between -0.5% to –0.8% reduction	eGFR ≥45 mL/minute/1.73 m2 no dosage adjustment necessary eGFR 25 to <45 not recommended
Empagliflozin	Jardiance	DM, Type 2 HF	Up to -0.8% reduction	eGFR ≥30 mL/minute/1.73 m2: No dosage adjustment necessary eGFR <30 mL/minute/1.73 m2 Not recommended
Ertugliflozin	Steglatro	DM, Type 2	5 mg: -0.7% 15 mg: -0.8%	eGFR ≥45 mL/minute/1.73 m2: No dosage adjustment necessary eGFR <45 mL/minute/1. 73 m2 Not recommended,

Table: GLP-1 Receptor Agonists

Drug Name	Brand Name	Labeled Indications	A1c Reduction	Average Weight Reduction
Liraglutide	Victoza	DM, Type 2	1.8 mg: -1.0% – -1.5%	In conjunction with metformin, avg 6.2 lbs
Semaglutide	Ozempic	DM, Type 2	0.5 mg: -1.4% 1.0 mg: -1.6% 2.0mg: 2.2%	0.5 mg: 8 lb 1.0 mg: 10-12 lb 2 mg: 14 lb
Semaglutide (oral)	Rybelsus	DM, Type 2	7 mg: -1.0% 14 mg: -1.3%	7 mg: 5 lbs 14 mg: 8 lbs
Lixisenatide	Adlyxin	DM, Type 2	Between -0.73% and -0.85%	7.1 lbs
Tirzepatide	Mounjaro	DM, Type 2	5 mg: -2.0% 10 mg: -2.2 % 15 mg: -2.3 %	In conjunction with Metformin 5 mg: 16.8 lbs 10 mg: 20.5 lbs 15 mg: 24.7 lbs
Exenatide	Bydureon; Byetta	DM, Type 2	Between -1.1% and -1.4%	Average of 3 lb weight reduction
Dulaglutide	Trulicity	DM, Type 2	1.5 mg: -1.5% 3.0 mg: -1.6% 4.5 mg: -1.8%	1.5 mg: 6.6 lb 3.0 mg: 8.4 lb 4.5 mg: 10.1 lb

Additionally, the ADA guidelines recommend proper categorization of patients with CKD by measuring albuminuria along with GFR, and to treat them accordingly. Following albuminuria when on treatment with goal reduction by 30% or more is recommended. Finerenone (Kerendia), a nonsteroidal mineralocorticoid (Aldosterone) receptor antagonist, has been added as a recommendation for patients with albuminuric diabetic kidney disease to reduce CKD progression and heart failure risk. If patients do not have ASCVD, CKD or CHF, along with metformin if tolerated and lifestyle modifications, the choice for next agents should be based on risks of hypoglycemia, obesity treatment and socioeconomic restraints.

Diabetes Technology

The new guidelines have strengthened the recommendations for the use of continuous glucose monitoring (CGM). Real-time CGM or intermittently scanned CGM is strongly recommended for diabetes management in adults on multiple daily insulin injections or insulin pumps. The guidelines now also recommend personal CGM for adults on basal insulin. The ADA also has included Time in Range (TIR) from CGM data along with HgbA1C to assess glycemic status and make therapeutic decisions. The goal for time in range continues to be 70 % or more.

Available Personal CGMs

CGM System	Sensor Placement	Length of Sensor Wear	SMBG Calibration	Approved for Insulin Dosing	Insulin Pump Integration	MARD, % (Mean Absolute Relative Difference)	Alarm
Real time CGM
Dexcom G6	SC	10 days	None required	Yes	Yes	9	Yes
Medtronic Guardian Sensor 3	SC	7 days	≥2x/day	No	Yes	9.6-10.5	Yes
Eversense	Implantable	180 days	≥2x/day	No	No	8.8	Yes
Intermittently Scanned CGM
FreeStyle Libre	SC	14 days	None required	Yes	No	10 days: 9.7 14 days: 9.4	No
FreeStyle Libre 2	SC	14 days	None required	Yes	No	Adults: 9.2 Children: 9.7	Yes

Longo. Diabetes Spectr. 2019;32:183. ascensiadiabetes.com/eversense/. FreeStyle Libre 2 User Manual.

Available Professional CGMs:

CGM System	Blinded	Sensor Placement	Length of Sensor Wear	SMBG	Reusable Sensor	(Mean Absolute Relative Difference)
Medtronic iPro 2	Yes	SC	Seven 24-hr periods	Every 12 hr for system uploading	Yes	13.6
Dexcom G6 Pro	Yes or no	SC	10 days	None required	No	9
FreeStyle Libre Pro	Yes	SC	14 days	None required	No	12.3

Adapted from: Longo. Diabetes Spectr. 2019;32:183. Chamberlain. Role of Continuous Glucose Monitoring in Diabetes Treatment. 2018. Hirsch. Clin Diabetes. 2019;37:150. provider.dexcom.com/products/dexcom-g6-pro#key-features

Expansion of Care Models

The new ADA standards emphasize the importance of creating sustainable care team modeling that is patient-centered. Using the SMART goals management plan, shared decision-making through empowering patients, assessing psychosocial factors and creating management programs with follow-up are some of the recommendations.

Diabetes is a chronic and complex condition. For our patients with low health literacy, lack of access to easy-to-understand information can lead to treatment failure. ADA guidelines have promoted individualization of care in previous iterations and continue to support health promotion with changes including the addition of a “Health Literacy and Numeracy” subsection.

The 2022 ADA standards of care recommend a true patient-centered approach for managing diabetes. Personalized and individualized medicine is the future.