Personalized Type 2 Diabetes Management: An Update on Recent Advances and Recommendations

Figures & data

Figure 1 Personalized diabetes care. This figure summarizes the key considerations that are needed when contemplating the choice of diabetes pharmacotherapy for a patient with T2D.

Figure 2 Therapeutic strategies for T2DM during time. This figure summarizes the key therapeutic strategies employed for people with T2D at different stages.

Abbreviations: IFG, impaired fasting glucose; IGT, impaired glucose tolerance; SGLT2i, sodium-glucose cotransporter-2 inhibitors; GLP-1RA, glucagon-like peptide-1 receptor analogue.

Table 1 Phenotypic Characteristics and Prevalence in the ANDIS (All New Diabetics in Scania) Cohort

Subgroup	Phenotypic Characteristics	Prevalence
Severe autoimmune diabetes (SAID)	Early-onset disease, relatively low BMI, poor metabolic control, insulin deficiency, and presence of GADA	6.5%
Severe insulin-deficient diabetes (SIDD)	Low age at onset, relatively low BMI, low insulin secretion (HOMA2-B index), poor metabolic control, and GADA negative	17.5%
Severe insulin-resistant diabetes (SIRD)	Insulin resistance (high HOMA2-IR index) and high BMI	15.3%
Mild obesity-related diabetes (MOD)	Obesity but not by insulin resistance	21.6%
Mild age-related diabetes (MARD)	Older than patients in other clusters, but modest metabolic derangements	39.1%

Note: Data from Ahlqvist et al.²⁰

Abbreviations: BMI, body mass index; GADA, glutamate decarboxylase antibodies: homeostatic model assessment 2 to estimate beta-cell function (HOMA2-B) and insulin resistance (HOMA2-IR).

Table 2 Summary of Type 2 Therapies: Effects on Cardiovascular Risk, Body Weight, Renal Use and Adverse Effects

Drug	Cardiovascular		Effect on Body Weight	Major Side Effects
	3P MACE	HF
Biguanide				GI disturbance, lactic acidosis
Metformin	Not done	Not done	Weight neutral
Sulphonylurea				Weight gain, hypoglycaemia
Gliclazide	Not done	Not done	Weight gain
Glimepiride	Not done	Not done	Weight gain
Thiazolidinedione				Oedema, heart failure, weight gain, fractures
Pioglitazone	Not done	Not done	Weight gain
DPP-IV inhibitor				GI disturbance, pancreatitis (uncommon)
Alogliptin^Citation36	↔	Not reported	Weight neutral
Saxagliptin^Citation37	↔	-	Weight neutral
Sitagliptin^Citation38	↔	↔	Weight neutral
Linagliptin^Citation39	↔	↔	Weight neutral
Vildagliptin	Not done	Not done	Weight neutral
SGLT-2 inhibitor				UTI, genital thrush
Canagliflozin^Citation40	+	+	Weight loss
Dapagliflozin^Citation41,Citation42	↔	+	Weight loss
Empagliflozin^Citation43–45	+	+	Weight loss
Ertugliflozin^Citation46	↔	+	Weight loss
GLP-1RA				GI disturbance, pancreatitis (uncommon)
Dulaglutide^Citation47	+	↔	Weight loss
Exenatide BD (Byetta)	No CVOT	No CVOT	Weight loss
Exenatide QW (Bydureon)^Citation48	↔	↔	Weight loss
Liraglutide^Citation49	+	↔	Weight loss
Lixisenatide^Citation50	↔	↔	Weight loss
Semaglutide^Citation51,Citation52	+	↔	Weight loss
Insulin^Citation57,Citation59	↔	↔	Weight gain	Weight gain, hypoglycaemia

Notes: + denotes superiority versus placebo, ↔ denotes non-inferiority versus placebo, - denotes inferiority versus placebo.

Abbreviations: 3P MACE 3, point major adverse cardiac events; DPP-IV, Dipeptidyl peptidase-4; eGFR, estimated glomerular filtration rate; GI, gastrointestinal; GLP-1RA, glucagon-like peptide-1 receptor analogue; HF, heart failure; SGLT-2, sodium-glucose co-transporter-2; UTI, urinary tract infection.

Table 3 An Empirical View of Personalized Care for a Patient with T2DM

Current Consideration
Does the available guidance apply to this individual?
Has the management plan been optimized as per guidance?
Does the therapy need to be modified for personalized reasons?
Optimize therapy according to clinical phenotype Optimize therapy for medical comorbidity (eg, cardiovascular, renal disease)
Are there biomarkers (eg, urinary C-peptide, GADA) to tailor therapy?
Are there genetic markers to tailor therapy (eg, MODY testing)?
Future considerations
Are there biomarkers to personalize therapy?
Are there genetic markers to personalize therapy?

Ahlqvist E, Storm P, Karajamaki A, et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endo. 2018;6:361–369. doi:10.1016/S2213-8587(18)30051-2

 PubMed Web of Science ®Google Scholar

White WB, Cannon CP, Heller SR, et al. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. New Engl J Med. 2013;369:1327–1335. doi:10.1056/NEJMoa1305889

 PubMed Web of Science ®Google Scholar

Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. New Engl J Med. 2013;369:1317–1326. doi:10.1056/NEJMoa1307684

 PubMed Web of Science ®Google Scholar

Green JB, Bethel MA, Armstrong PW, et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. New Engl J Med. 2015;373:232–242.

 PubMed Web of Science ®Google Scholar

Rosenstock J, Perkovic V, Johansen OE, et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk the CARMELINA Randomized Clinical Trial. JAMA-J Am Med Assoc. 2019;321:69–79. doi:10.1001/jama.2018.18269

 PubMed Web of Science ®Google Scholar

Neal B, Perkovic V, Matthews DR. Canagliflozin and cardiovascular and renal events in type 2 diabetes reply. New Engl J Med. 2017;377:2099. doi:10.1056/NEJMoa1611925

 PubMed Web of Science ®Google Scholar

Wiviott SD, Raz I, Sabatine MS. Dapagliflozin and cardiovascular outcomes in type 2 diabetes reply. New Engl J Med. 2019;380:1881–1882. doi:10.1056/NEJMoa1812389

 Web of Science ®Google Scholar

McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in patients with heart failure and reduced ejection fraction. New Engl J Med. 2019;381:1995–2008. doi:10.1056/NEJMoa1911303

 PubMed Web of Science ®Google Scholar

Cannon CP, Pratley R, Dagogo-Jack S, et al. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. New Engl J Med. 2020;383:1425–1435. doi:10.1056/NEJMoa2004967

 PubMed Web of Science ®Google Scholar

Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394:121–130. doi:10.1016/S0140-6736(19)31149-3

 PubMed Web of Science ®Google Scholar

Holman RR, Bethel MA, Mentz RJ, et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. New Engl J Med. 2017;377:1228–1239. doi:10.1056/NEJMoa1612917

 PubMed Web of Science ®Google Scholar

Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. New Engl J Med. 2016;375:311–322. doi:10.1056/NEJMoa1603827

 PubMed Web of Science ®Google Scholar

Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. New Engl J Med. 2015;373:2247–2257. doi:10.1056/NEJMoa1509225

 PubMed Web of Science ®Google Scholar

Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. New Engl J Med. 2016;375:1834–1844. doi:10.1056/NEJMoa1607141

 PubMed Web of Science ®Google Scholar

Husain M, Birkenfeld AL, Donsmark M, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. New Engl J Med. 2019;381:841–851. doi:10.1056/NEJMoa1901118

 PubMed Web of Science ®Google Scholar

Gerstein HC, Bosch J, Dagenais GR, et al. Basal insulin and cardiovascular and other outcomes in dysglycemia. New Engl J Med. 2012;367:319–328.

 PubMed Web of Science ®Google Scholar

Marso SP, McGuire DK, Zinman B, et al. Efficacy and safety of degludec versus glargine in type 2 diabetes. New Engl J Med. 2017;377:723–732. doi:10.1056/NEJMoa1615692

 PubMed Web of Science ®Google Scholar