IN BRIEF Caring for people with type 2 diabetes requires a patient-centered approach to treatment targets and medication regimens. Focusing on patients’ individual characteristics, needs, and treatment responses can improve compliance and clinical outcomes. Medication selection can be guided by the mechanisms of action, advantages, disadvantages, and costs of available options; patients’ behavioral and psychological variables, personal preferences, and socioeconomic status also should be taken into account. This article provides an overview of patient-centered and individualized diabetes management, offers pharmacological recommendations for specific clinical scenarios, and describes a complicated case illustrating the patient-centered approach in clinical practice.

The growing armamentarium of treatment options for type 2 diabetes has allowed clinicians to better target specific underlying pathophysiological defects associated with the disease. Traditionally, metformin, sulfonylureas, thiazolidinediones (TZDs), and insulin were the primary glucose-lowering agents prescribed. However, within the past decade and a half, newer agents targeting incretins and renal disposal of glucose have become available. Numerous factors must be taken into account when designing a treatment regimen. These include patient-specific factors such as the underlying pathogenesis of diabetes, BMI and risk of weight gain, risk of adverse effects such as hypoglycemia, and ability to administer and tolerate medications, as well as medication-specific factors such as efficacy, potency, and cost. Excellent comprehensive patient-centered algorithms for diabetes management are available and emphasize individualization of both glycemic targets and the selection of glucose-lowering agents (18).

The concept of patient-centered care has been described by many in the literature, but the exact definition is not completely clear. A review of the literature in 2000 found that most descriptions of this topic included five key concepts: 1) a biopsychosocial perspective (social and psychological influences on illness and behavior), 2) consideration of patients’ personal experience of illness, 3) shared power and responsibility (i.e., greater patient autonomy and participation in decision-making), 4) a collaborative patient-provider relationship (i.e., mutual trust and understanding of treatment needs and goals), and 5) the role of the personal qualities of the doctor (doctor subjectivity) (9). Patient-centered care in diabetes involves evaluating individual patients’ unique characteristics, preferences, and abilities to devise a personalized treatment plan and therapeutic goals. Working to better understand patients’ experience with taking diabetes medications, improve the patient-provider relationship to gain patients’ trust, and obtain necessary health care system support for providers can promote adherence to the medication regimen in diabetes (10).

Evidence supporting the use of patient-centered care is provided by the Diabetes Care in General Practice (DCGP) study (11). The DCGP looked at the effects of 6 years of intervention with structured personal care versus routine care of type 2 diabetes over a 19-year follow-up period. Structured personal care involved quarterly patient visits at which individualized treatment goals (A1C and glucose, blood pressure, and cholesterol levels) were set and followed up on, with physician supports such as prompting, feedback, clinical guidelines, and continuing medical education. At 19 years, DGCP intervention resulted in lower risks of myocardial infarction (MI) and any diabetes-related endpoint for patients. Analysis of a subset of DCGP patients with diabetes and concurrent psychiatric illness demonstrated that structured personal care for these patients resulted in lower risks for all-cause mortality, diabetes-related death, any diabetes-related endpoint, and MI (12).

Published algorithms for diabetes management recommend individualization of glycemic goals (18). The benefits of preventing or delaying progression of micro- and macro-vascular complications must be weighed against the risks of tight glycemic control, including hypoglycemia, adverse effects from medications, and cost.

The landmark U.K. Prospective Diabetes Study (UKPDS) (13,14) and the Kumamoto study (15) de-monstrated that intensive glycemic control aiming for an A1C of 7 and 6.5%, respectively, was beneficial in reducing the rate of micro-vascular complications. The impact of tight glycemic control on macrovascular complications is less certain. The UKPDS found a small, statistically nonsignificant (P = 0.052) reduction in the risk of MI with intensive treatment with insulin and sulfonylureas for 10 years (13). A significant reduction in risk of MI, diabetes-related death, and all-cause mortality was found only in a subset of overweight patients randomized to metformin in the UKPDS (14). However, as more events occurred during the additional 10-year follow-up of study (1997–2007), reductions in risk for MI and all-cause mortality did become apparent in the intensive treatment group (16).

The effects of intensive treatment on cardiovascular endpoints were specifically studied in three large trials: ACCORD (Action to Control Cardiovascular Risk in Diabetes) (17), ADVANCE (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation) (18), and VADT (Veterans Affairs Diabetes Trial) (19). ACCORD and VADT targeted a normal A1C (<6%), whereas ADVANCE targeted an A1C ≤6.5%. The duration of ADVANCE and VADT was 5 years; ACCORD was planned to run for ∼5 years, but its intensive treatment arm was terminated after 3.5 years because of a higher mortality rate in that group. Those receiving intensive therapy were then transitioned to the standard therapy group until the completion of the study at 5 years. ADVANCE and VADT did not find any significant effect of intensive treatment on the rate of major cardiovascular events or death but did find a benefit of tight glycemic control on the development and progression of nephropathy (18,19). ACCORD also did not find a significant reduction in major cardiovascular events, but its unexpected finding of a 22% relative increase in total mortality, mainly due to an increase in death from cardiovascular causes, in the intensive group emerged 1–2 years after randomization (17).

Based on the results of these trials, the general consensus of guidelines and expert opinion is to recommend an A1C target of 7% for most patients, although a target of <6.5 or >8% may be appropriate for certain patients depending on their characteristics and comorbidities (24,20). Many algorithms have been published regarding how to individualize glycemic targets and what factors to consider (58), the most comprehensive and widely used of which can be found in an American Diabetes Association (ADA)/European Asso-ciation for the Study of Diabetes (EASD) joint position statement (2,3), the ADA’s Standards of Medical Care in Diabetes (4), and a consensus statement and algorithm published by the American Association of Clinical Endocrinologists (AACE) and American College of Endocrinology (ACE) (1). The ADA/EASD position statement and ADA standards recommend determining the stringency of glycemic control based on patients’ attitude, treatment-associated risks (including hypoglycemia), disease duration, life expectancy, comorbidities, vascular complications, and resources. More stringent control is felt to be reasonable in healthy patients without cardiovascular disease (CVD) if it can be achieved without significant hypoglycemia, whereas higher A1C targets should be used in patients with severe hypoglycemia, extensive complications and comorbidities, and limited life expectancy. The AACE/ACE algorithm similarly recommends taking patients’ characteristics into account but has a more stringent A1C goal of ≤6.5% for most patients and is more aggressive with initiating and adding glucose-lowering agents. The AACE/ACE algorithm recommends targeting a higher A1C of 7–8% for patients with hypoglycemia, comorbidities, macrovascular disease, advanced renal disease, or limited life expectancy (1).

The choice of agent(s) to use must be based on patient-specific needs, keeping in mind the underlying pathogenesis of patients’ diabetes, as well as their BMI and risk of weight gain, risk of adverse treatment effects (including hypoglycemia), and ability to administer and tolerate medications. The efficacy and potency of medications and their costs also must be considered.

Therapies targeting insulin resistance in the muscle and liver (metformin and TZDs) and β-cell insufficiency (sulfonylureas, meglitinides, and insulin) were considered the primary treatment options for type 2 diabetes until the past decade, when newer therapies with alternate targets became available. Newer therapies target the pathophysiological defects of incretin deficiency, excess glucagon production, and increased renal glucose reabsorption.

Incretin-based therapies include the glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. GLP-1 receptor agonists stimulate glucose-dependent insulin secretion, suppress postmeal glucagon secretion, slow gastric emptying, increase satiety, and potentially stimulate insulin gene transcription and β-cell growth (21). These injectables are available as short-acting agents given daily or long-acting, once-weekly formulations. The short-acting agents include twice-daily exenatide, once-daily liraglutide, and once-daily lixisenatide. Long-acting once-weekly formulations include exenatide extended release, albiglutide, and dulaglutide.

Benefits of GLP-1 receptor agonists include A1C lowering of 1–2%, no hypoglycemia when used alone, and weight loss of 1.5–4 kg over 24–52 weeks (22). Two recent trials also demonstrated a reduction in cardiovascular risk and nephropathy with liraglutide (23) and semaglutide, a new drug in this class that has not yet been approved by the U.S. Food and Drug Administration (FDA) (24). The main drawbacks are concerns about the potential risk of pancreatitis and pancreatic cancer (25,26), C cell hyperplasia and tumors (27), and gastrointestinal side effects of nausea and vomiting.

An alternate method of increasing GLP-1 is inhibition of DPP-4, the enzyme that breaks down GLP-1. Four DPP-4 inhibitors are approved for use in the United States: sitagliptin, saxagliptin, linagliptin, and alogliptin. Compared to GLP-1 receptor agonists, agents in this medication class have modest glycemic efficacy (A1C reduction of 0.5–0.9%), are weight neutral, and do not cause nausea.

Pancreatitis has also been reported with the use of DPP-4 inhibitors. Other concerns include an FDA-issued warning in 2015 regarding severe joint pain with DDP-4 inhibition. In terms of cardiovascular risk, no increased risk of cardiovascular events or heart failure was found with any of drugs (2831) except saxagliptin, which was associated with a higher rate of hospitalization for heart failure compared to placebo (28).

The newest class of glucose-lowering medications are the sodium–glucose cotransporter 2 (SGLT2) inhibitors. These medications have a unique, insulin-independent me-chanism of action that involves blockade of renal reabsorption of glucose via SGLT2 in the proximal convoluted tubule of the kidney (32). Canagliflozin, dapagliflozin, and empagliflozin are the three available drugs in this class.

Benefits of SGLT2 inhibitors include a low risk of hypoglycemia, weight loss of 2–3 kg over 24–52 weeks, and blood pressure–lowering effects (33). The main adverse effects are increases in genital mycotic and urinary tract infections. In addition, because of the drugs’ diuretic effect, symptoms of volume depletion have been described, particularly in elderly patients who may already be on a diuretic or other antihypertensive agent(s). Recently, additional adverse events, including euglycemic diabetic ketoacidosis with drugs from this class (34), an increase in bone fractures with canagliflozin (35), and toe/metatarsal amputations with canagliflozin (36), have been reported.

In terms of cardiovascular effects, empagliflozin was found to lower rates of death from CVD and hospitalization for heart failure (37), and canagliflozin showed a reduction in risks of cardiovascular events and heart failure hospitalization (36). Findings from the EMPA-REG OUTCOME (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) trial (37) led to the FDA’s approval of a new indication for the agent to reduce the risk of cardiovascular death in patients with type 2 diabetes and CVD, making empagliflozin the first type 2 diabetes medication approved for this indication. Both empagliflozin and canagliflozin were found to slow the progression of albuminuria, the reduction in estimated glomerular filtration rate (eGFR), and the development of end-stage renal disease (ESRD) and to decrease death from renal causes (36,38).

Because these newer agents have a noninsulin-dependent mechanism of action, they tend not to increase weight and do not cause hypoglycemia on their own. The advantages of weight neutrality and even possible weight loss, decreased risk of hypoglycemia, and specific benefits such as reduction in cardiovascular risk and progression of kidney disease make these agents attractive options as second- or third-line therapies after metformin, or even as first-line therapy if metformin is contraindicated. However, the main disadvantage of these medications is their high cost. The potential benefits of incretin-based agents (GLP-1 receptor agonists and DPP-4 inhibitors) and SGLT2 inhibitors must be weighed against their expense, less extensive clinical use to date, and infrequent but potentially serious adverse events.

The ADA/EASD algorithm recommends metformin as first-line therapy but is not prescriptive with regard to second- or third-line choices of agents. This algorithm recommends taking into account medications’ cellular mechanism, primary physiological action, advantages, disadvantages, and cost when making a selection for a given patient (2,3,39). Specific advantages noted in this algorithm for older medications (metformin and sulfonylureas) include extensive experience, low cost, and evidence of macrovascular (metformin) and microvascular (sulfonylureas) risk reduction in the UKPDS (2,3,39). TZDs, although no longer commonly used because of concerns about increased MI and heart failure risk, still have a place in treatment in the ADA/EASD algorithm because of their low cost, low hypoglycemia risk, durability, and beneficial effects on lipids (2,3,39). Newer agents such as GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 inhibitors are noted by ADA/EASD to have the advantages of no hypoglycemia and weight loss or weight neutrality, but these benefits have to be weighed against their high costs and rare but potentially serious adverse associations.

The AACE/ACE glycemic control algorithm similarly uses a patient-centered approach, but is stratified based on the initial A1C and is more prescriptive. Pharmacological therapy with one agent is recommended for patients who present with an A1C <7.5%, whereas two agents are advised if initial A1C is ≥7.5%. Insulin is recommended if A1C is >9% with symptoms of hyperglycemia (1).

This more prescriptive algorithm ranks the medications based on strength of the expert consensus recommendation; those with fewer adverse events, especially weight gain and hypoglycemia, and greater possible benefits are listed higher. Metformin is considered the first-line therapy, with a suggested second-line hierarchy of GLP-1 receptor agonists, SGLT2 inhibitors, and then DPP-4 inhibitors. TZDs and sulfonylureas are much lower on the hierarchy of usage (1).

In addition to the pharmacological profile of the glucose-lowering agents, patients’ behavioral and psychological variables, as well as their health status and comorbidities need to be taken into account when choosing glucose-lowering therapies.

Behavioral and psychological variables that may affect the choice of medications include patients’ degree of motivation, acceptable level of treatment intensity, acceptance of and ability to administer injections, responses to and tolerance of past medications, support system, food and cultural preferences, level of physical activity, and socio-economic status. Health status and comorbidities that may affect treatment decisions include patients’ age, duration of diabetes, tendency to experience hypoglycemia, hypoglycemia unawareness, and severity of hyperglycemia, as well as the presence of overweight/obesity, macrovascular disease, renal impairment, liver dysfunction, or microvascular complications.

Overweight and Obesity

Choosing weight-neutral or weight loss–inducing medications for overweight or obese patients with diabetes is in accordance with the ADA/EASD guidelines (24) and Endocrine Society guidelines on the pharmacological management of obesity (40). Metformin, GLP-1 receptor agonists, and SGLT2 inhibitors are recommended for their dual benefit of improved glycemic control and potential weight loss. DPP-4 inhibitors are weight neutral and can also be considered. Other glucose-lowering agents that do not induce weight gain and are not described above (i.e., α-glucosidase inhibitors and pramlintide, an amylin mimetic) could be considered but typically are not used because of their side effects, modest efficacy, and frequency of administration.

Medications that can exacerbate weight issues include sulfonylureas and TZDs, which are associated with weight gain of 1.5–2.5 kg over 10 years (13) and 3 kg over 6 months (41), respectively. Insulin increased weight on average by 7 kg over 10 years in the UKPDS (13). If insulin is indicated, detemir may be a better option in overweight or obese patients because weight gain was found to be less with detemir than with NPH or glargine insulin, while no difference was found in weight gain between NPH and glargine (42).

High Risk for Hypoglycemia or Presence of Hypoglycemia Unawareness

Noninsulin-dependent medications such as metformin, SGLT2 inhibitors, GLP-1 receptor agonists, or DPP-4 inhibitors are preferred for patients who are prone to hypoglycemia or have hypoglycemia unawareness. Insulin secretagogues should be avoided. If insulin is needed, levemir and degludec have a lower incidence of hypoglycemia than glargine or NPH (41,43).

Renal Insufficiency or ESRD

DPP-4 inhibitors can be used in patients with renal insufficiency or ESRD. Dose reduction is recommended based on creatinine clearance for sitagliptin, saxagliptin, and alogliptin, whereas no dose adjustment is necessary for linagliptin. Metformin can now be used for patients with a lower eGFR but should be discontinued if the eGFR is <30 mL/min/1.73 m2 and continued with a dose reduction and assessment of risk if the eGFR is 30–45 mL/min/1.73 m2 (44). SGLT2 inhibitors can be used if the eGFR is >45–60 mL/min/1.73 m2, depending on the specific agent. They should be used cautiously in renal insufficiency because cases of acute kidney injury requiring hospitalization or dialysis have been reported to the FDA. Long-acting insulin secretagogues should be avoided because of accumulation of active metabolites and increased risk of hypoglycemia. Insulin doses may need to be reduced because of decreased elimination.

CVD

For patients with CVD, liraglutide, semaglutide (when it becomes available), canagliflozin, or empagliflozin have been shown to reduce risk of cardiovascular outcomes and death from cardiovascular causes (23,24,36,37). Sulfonylureas should be avoided given their uncertain impact and potential negative effect on cardiovascular outcomes. The TZD rosiglitazone, which has generally fallen out of favor, has uncertain effects on risk of MI and should be avoided (45,46).

Heart Failure

If heart failure is present, TZDs should be avoided given their association with fluid retention and increased risk of heart failure (44). Saxagliptin should also be avoided because patients taking it were found to have a higher rate of hospitalization for heart failure (28). In contrast, empagliflozin significantly reduced the risk of hospitalization for heart failure and should be considered in heart failure patients (37). Liraglutide was also found to result in fewer hospitalizations for heart failure compared to placebo, although the difference was not statistically significant (23).

Difficulty Complying With Injections

When injections are needed in patients who have problems with compliance or fear of injections, simplifying the regimen with a long-acting injectable such as a once-weekly GLP-1 receptor agonist and once-daily basal insulin or using premixed insulin or U-500 insulin twice daily are options.

Lack of Insurance or Financial Limitations

Physicians are often limited in their prescribing by patients’ lack of adequate insurance coverage or high copayment requirements on prescription medications. In these cases, the least expensive oral agents available as generics are metformin, sulfonylureas, or TZDs. The least expensive insulins are NPH and regular insulin. Vials also tend to be more cost-effective than insulin pens.

If brand-name medications are prescribed, patient assistance programs and savings cards are available. AACE has launched a patient prescription savings directory that is available online at http://prescriptionhelp.aace.com. This directory includes a list of links to patient drug assistance and charitable copayment assistance organizations offering reduced or no-cost endocrine medications. Prescription assistance information on the ADA website is another excellent source for patients and physicians and can be accessed at http://www.diabetes.org/living-with-diabetes/health-insurance/prescription-assistance.html. This site includes information on drug discount programs and databases, in addition to financial assistance programs offered by pharmaceutical companies. An excellent website and mobile app that compares prices and discounts from more than 60,000 U.S. pharmacies is https://www.goodrx.com.

Some retailers offer free or discounted diabetes medications. For example, Meijer stores dispense metformin at no cost with a prescription (47). The stores of SpartanNash (Family Fare, D and W Fresh Market, Family Fresh Market, and VG’s Grocery) have generic metformin, glipizide, glyburide, and glimepiride at no cost and also sell 1- and 3-month supplies of generic medications for $4 and $10, respectively (4851). Walmart and Target also offer $4 (1-month) and $10 (3-month) generic medications (52,53). A recent Internet article available on www.verywell.com lists several additional stores that offer free and low-cost prescription drugs (54).

The following case study illustrates the patient-centered approach to setting treatment targets and determining a therapeutic regimen for type 2 diabetes.

Presentation

Judy, a 55-year-old woman with poorly controlled type 2 diabetes since the age of 35 years, hypertension, and hyperlipidemia, presented to the hospital with a complaint of episodic chest pain for 1 month. Cardiac catheterization revealed severe triple-vessel coronary artery disease (CAD) necessitating elective four-vessel coronary artery bypass grafting. Her A1C at admission was 10.2%. Additional complications included proliferative diabetic retinopathy treated with panretinal photocoagulation and diabetic nephropathy (urine albumin/creatinine ratio 241 mg/g and eGFR 80 mL/min/1.73 m2).

Her diabetes was treated with metformin and glipizide. She had declined insulin in the past because of her job as a bus driver and the need to apply for a medical waiver if insulin were initiated.

Judy also had a recent diagnosis of rheumatoid arthritis (RA) treated with methotrexate. The RA caused pain and stiffness in her hands, resulting in difficulty checking her blood glucose.

Basal-bolus insulin therapy was initiated on admission to the hospital for cardiac surgery, and her oral glucose-lowering agents were stopped. Her discharge diabetes regimen included glargine 15 units every morning and aspart 2–4 units with each meal based on a correction scale. (After surgery, she was on medical leave from her job and not driving, so the use of insulin was not a problem.)

Judy presented to the clinic 3 months after discharge for help in managing her diabetes. With the insulin and significant dietary improvements, she lowered her A1C to 6.2%. Her main concerns now include:

  • Weight gain of 20 lb since hospital discharge, despite improvement in diet, resulting in a BMI of 31.2 kg/m2

  • Stiff, swollen hands from RA, resulting in difficulty with injecting multiple times daily and checking blood glucose

  • The need for a noninsulin regimen if possible, in case she can return to her previous work as a bus driver

  • Symptoms of sweating and hunger occurring about once a week before dinner and relieved by juice and crackers

Questions to Consider

  1. What is the optimal level of glycemic control for Judy?

  2. What are her treatment options?

  3. What factors should be considered when determining which medications to prescribe for her?

Developing a Treatment Plan

For Judy, a reasonable A1C goal would be 7%. She is a motivated patient who complies with her diabetes regimen but has characteristics that increase her risk of hypoglycemia. These characteristics include difficulty with monitoring her glucose, a long duration of disease, and multiple comorbidities, including severe CAD. Her current A1C of 6.2% is too stringent given her comorbidities and symptoms of sweating and hunger that could indicate hypoglycemia.

With regard to treatment, she likely does not require multiple daily insulin injections because she is on a very low dose of insulin, her A1C is <6.5%, and she is likely experiencing hypoglycemia. To determine which medications would be best for Judy, several factors should be taken into consideration. First, she mentions that she has difficulty with injections because of her RA. Based on this, injectable agents, including insulin, should be avoided or limited to as few injections as possible. Second, she complains of weight gain with insulin and currently has a BMI in the obese range. Medications that are weight neutral or associated with weight loss such as metformin, GLP-1 receptor agonists, SGLT2 inhibitors, or DPP-4 inhibitors should be preferred. Because she has CAD, empagliflozin, canagliflozin, and/or liraglutide would be ideal choices based on recent cardiovascular outcomes trials demonstrating a decrease in cardiovascular risk with their use (23,36,37). These agents were also found to have a beneficial effect on nephropathy (23,36,38), a complication also present in this patient.

Judy and her provider discussed the treatment options, and she expressed interested in restarting metformin and adding liraglutide to her regimen. She chose liraglutide over the SGLT2 inhibitors because of its greater A1C-lowering efficacy and possibly greater associated weight loss. If a third agent is needed, reasonable choices would be empagliflozin or canagliflozin because her eGFR is >45 mL/min/1.73 m2.

The case study presented above illustrates the importance of taking a patient-centered approach in the management of type 2 diabetes. Treatment of diabetes for this patient was complicated by hypoglycemia, difficulty with multiple injections, obesity, and a history of CAD and nephropathy. Based on these factors, glucose-lowering agents with potential beneficial effects on CVD and nephropathy and a low likelihood of hypoglycemia and weight gain were considered.

Current algorithms recognize that one size does not fit all in diabetes care. Tailoring glycemic goals and treatment regimens to patient-specific needs and preferences is associated with increased patient satisfaction, improved patient-provider relationship and communication, and enhanced patient well-being without compromising glycemic control (55).

No potential conflicts of interest relevant to this article were reported.

S.L. was the sole author and is the guarantor of this work and takes responsibility for the integrity and accuracy of the manuscript.

1.
Garber
AJ
,
Abrahamson
MJ
,
Barzilay
JI
, et al.;
American Association of Clinical Endocrinologists (AACE); American College of Endocrinology (ACE)
.
Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm—2017: executive summary
.
Endocr Pract
2017
;
23
:
207
238
2.
Inzucchi
SE
,
Bergenstal
RM
,
Buse
JB
, et al
.
Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes
.
Diabetes Care
2015
;
38
:
140
149
3.
Inzucchi
SE
,
Bergenstal
RM
,
Buse
JB
, et al.;
American Diabetes Association (ADA); European Association for the Study of Diabetes (EASD)
.
Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)
.
Diabetes Care
2012
;
35
:
1364
1379
4.
American Diabetes Association
.
Glycemic targets. Sec. 6. in Standards of Medical Care in Diabetes—2017
.
Diabetes Care
2017
;
40
(
Suppl. 1
):
S48
S56
5.
Pozzilli
P
,
Leslie
RD
,
Chan
J
, et al
.
The A1C and ABCD of glycaemia management in type 2 diabetes: a physician’s personalized approach
.
Diabetes Metab Res Rev
2010
;
26
:
239
244
6.
Del Prato
S
,
LaSalle
J
,
Matthaei
S
,
Bailey
CJ
;
Global Partnership for Effective Diabetes Management
.
Tailoring treatment to the individual in type 2 diabetes: practical guidance from the Global Partnership for Effective Diabetes Management
.
Int J Clin Pract
2010
;
64
:
295
304
7.
Bailey
CJ
,
Aschner
P
,
Del Prato
S
,
LaSalle
J
,
Ji
L
,
Matthaei
S
;
Global Partnership for Effective Diabetes Management
.
Individualized glycaemic targets and pharmacotherapy in type 2 diabetes
.
Diab Vasc Dis Res
2013
;
10
:
397
409
8.
Subramanian
S
,
Hirsch
IB
.
Personalized diabetes management: moving from algorithmic to individualized therapy
.
Diabetes Spectr
2014
;
27
:
87
91
9.
Mead
N
,
Bower
P
.
Patient-centredness: a conceptual framework and review of the empirical literature
.
Soc Sci Med
2000
;
51
:
1087
1110
10.
Schwartz
DD
,
Stewart
SD
,
Aikens
JE
,
Bussell
JK
,
Osborn
CY
,
Safford
MM
.
Seeing the person, not the illness: promoting diabetes medication adherence through patient-centered collaboration
.
Clin Diabetes
2017
;
35
:
35
42
11.
Hansen
LJ
,
Siersma
V
,
Beck-Nielsen
H
,
de Fine Olivarius
N
.
Structured personal care of type 2 diabetes: a 19 year follow-up of the study Diabetes Care in General Practice (DCGP)
.
Diabetologia
2013
;
56
:
1243
1253
12.
Larsen
JR
,
Siersma
VD
,
Davidsen
AS
,
Waldorff
FB
,
Reventlow
S
,
de Fine Olivarius
N
.
The excess mortality of patients with diabetes and concurrent psychiatric illness is markedly reduced by structured personal diabetes care: a 19-year follow up of the randomized controlled study Diabetes Care in General Practice (DCGP)
.
Gen Hosp Psychiatry
2016
;
38
:
42
52
13.
U.K. Prospective Diabetes Study Group
.
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)
.
Lancet
1998
;
352
:
837
853
14.
U.K. Prospective Diabetes Study Group
.
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)
.
Lancet
1998
;
352
:
854
865
15.
Ohkubo
Y
,
Kishikawa
H
,
Araki
E
, et al
.
Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study
.
Diabetes Res Clin Pract
1995
;
28
:
103
117
16.
Holman
RR
,
Paul
SK
,
Bethel
MA
,
Matthews
DR
,
Neil
HA
.
10-year follow-up of intensive glucose control in type 2 diabetes
.
N Engl J Med
2008
;
359
:
1577
1589
17.
Action to Control Cardiovascular Risk in Diabetes Study Group
;
Gerstein
HC
,
Miller
ME
,
Byington
RP
, et al
.
Effects of intensive glucose lowering in type 2 diabetes
.
N Engl J Med
2008
;
358
:
2545
2559
18.
ADVANCE Collaborative Group
;
Patel
A
,
MacMahon
S
,
Chalmers
J
, et al
.
Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes
.
N Engl J Med
2008
;
358
:
2560
2572
19.
Duckworth
W
,
Abraira
C
,
Moritz
T
, et al.;
VADT Investigators
.
Glucose control and vascular complications in veterans with type 2 diabetes
.
N Engl J Med
2009
;
360
:
129
139
20.
Turnbull
FM
,
Abraira
C
,
Anderson
RJ
, et al
.
Intensive glucose control and macrovascular outcomes in type 2 diabetes
.
Diabetologia
2009
;
52
:
2288
2298
21.
Chia
CW
,
Egan
JM
.
Incretin-based therapies in type 2 diabetes mellitus
.
J Clin Endocrinol Metab
2008
;
93
:
3703
3716
22.
Madsbad
S
.
Review of head-to-head comparisons of glucagon-like peptide-1 receptor agonists
.
Diabetes Obes Metab
2016
;
18
:
317
332
23.
Marso
SP
,
Daniels
GH
,
Brown-Frandsen
K
, et al.;
LEADER Steering Committee; LEADER Trial Investigators
.
Liraglutide and cardiovascular outcomes in type 2 diabetes
.
N Engl J Med
2016
;
375
:
311
322
24.
Marso
SP
,
Bain
SC
,
Consoli
A
, et al.;
SUSTAIN-6 Investigators
.
Semaglutide and cardiovascular outcomes in patients with type 2 diabetes
.
N Engl J Med
2016
;
375
:
1834
1844
25.
Butler
AE
,
Campbell-Thompson
M
,
Gurlo
T
,
Dawson
DW
,
Atkinson
M
,
Butler
PC
.
Marked expansion of exocrine and endocrine pancreas with incretin therapy in humans with increased exocrine pancreas dysplasia and the potential for glucagon-producing neuroendocrine tumors
.
Diabetes
2013
;
62
:
2595
2604
26.
European Medicines Agency
.
Assessment report for GLP-1 based therapies [Internet]
.
27.
Bjerre Knudsen
L
,
Madsen
LW
,
Andersen
S
, et al
.
Glucagon-like peptide-1 receptor agonists activate rodent thyroid C-cells causing calcitonin release and C-cell proliferation
.
Endocrinology
2010
;
151
:
1473
1486
28.
Scirica
BM
,
Bhatt
DL
,
Braunwald
E
;
SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus
.
N Engl J Med
2013
;
369
:
1317
1326
29.
White
WB
,
Cannon
CP
,
Heller
SR
, et al.;
EXAMINE Investigators
.
Alogliptin after acute coronary syndrome in patients with type 2 diabetes
.
N Engl J Med
2013
;
369
:
1327
1335
30.
Green
JB
,
Bethel
MA
,
Armstrong
PW
, et al.;
TECOS Study Group
.
Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes
.
N Engl J Med
2015
;
373
:
232
242
31.
Rosenstock
J
,
Marx
N
,
Neubacher
D
, et al
.
Cardiovascular safety of linagliptin in type 2 diabetes: a comprehensive patient-level pooled analysis of prospectively adjudicated cardiovascular events
.
Cardiovasc Diabetol
2015
;
14
:
57
32.
Cangoz
S
,
Chang
YY
,
Chempakaseril
SJ
, et al
.
The kidney as a new target for antidiabetic drugs: SGLT2 inhibitors
.
J Clin Pharm Ther
2013
;
38
:
350
359
33.
Raskin
P
.
Sodium-glucose cotransporter inhibition: therapeutic potential for the treatment of type 2 diabetes mellitus
.
Diabetes Metab Res Rev
2013
;
29
:
347
356
34.
Rosenstock
J
,
Ferrannini
E
.
Euglycemic diabetic ketoacidosis: a predictable, detectable, and preventable safety concern with SGLT2 inhibitors
.
Diabetes Care
2015
;
38
:
1638
1642
35.
Watts
NB
,
Bilezikian
JP
,
Usiskin
K
, et al
.
Effects of canagliflozin on fracture risk in patients with type 2 diabetes mellitus
.
J Clin Endocrinol Metab
2016
;
101
:
157
166
36.
Neal
B
,
Perkovic
V
,
Mahaffey
KW
, et al.;
CANVAS Program Collaborative Group
.
Canagliflozin and cardiovascular and renal events in type 2 diabetes
.
N Engl J Med
2017
;
377
:
644
657
37.
Zinman
B
,
Wanner
C
,
Lachin
JM
, et al.,
EMPA-REG OUTCOME Investigators
.
Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes
.
N Engl J Med
2015
;
373
:
2117
2128
38.
Wanner
C
,
Inzucchi
SE
,
Lachin
JM
, et al.;
EMPA-REG OUTCOME Investigators
.
Empagliflozin and progression of kidney disease in type 2 diabetes
.
N Engl J Med
2016
;
375
:
323
334
39.
American Diabetes Association
.
Pharmacologic approaches to glycemic treatment. Sec. 8 in Standards of Medical Care in Diabetes—2017
.
Diabetes Care
2017
;
40
(
Suppl. 1
):
S64
S74
40.
Apovian
CM
,
Aronne
LJ
,
Bessesen
DH
, et al.;
Endocrine Society
.
Pharmacological management of obesity: an Endocrine Society clinical practice guideline
.
J Clin Endocrinol Metab
2015
;
100
:
342
362
41.
Chiquette
E
,
Ramirez
G
,
Defronzo
R
.
A meta-analysis comparing the effect of thiazolidinediones on cardiovascular risk factors
.
Arch Intern Med
2004
;
164
:
2097
2104
42.
Strandberg
AY
,
Khanfir
H
,
Mäkimattila
S
,
Saukkonen
T
,
Strandberg
TE
,
Hoti
F
.
Insulins NPH, glargine, and detemir and risk of severe hypoglycemia among working-age adults
.
Ann Med
2017
;
49
:
357
364
43.
Ratner
RE
,
Gough
SC
,
Mathieu
C
, et al
.
Hypoglycaemia risk with insulin degludec compared with insulin glargine in type 2 and type 1 diabetes: a pre-planned meta-analysis of phase 3 trials
.
Diabetes Obes Metab
2013
;
15
:
175
184
44.
U.S. Food and Drug Administration
.
FDA drug safety communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function [Internet]
.
Available from https://www.fda.gov/Drugs/DrugSafety/ucm493244.htm. Accessed 21 September 2017
45.
Nissen
SE
,
Wolski
K
.
Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes
.
N Engl J Med
2007
;
356
:
2457
2471
46.
Home
PD
,
Pocock
SJ
,
Beck-Nielsen
H
, et al.;
RECORD Study Group
.
Rosiglitazone evaluated for cardiovascular outcomes: an interim analysis
.
N Engl J Med
2007
;
357
:
28
38
47.
Meijer
.
Free prescriptions [Internet]
.
48.
Family Fare Supermarkets
.
Free and low-cost prescriptions [Internet]
.
49.
D and W Fresh Market
.
PDF of free medications available and PDF of $4 or $10 medications available [Internet]
.
Available from https://www.shopdwfreshmarket.com/yes-card. Accessed 21 September 2017
50.
VG’s grocery
.
PDF of free medications available and PDF of $4 or $10 medications available [Internet]
.
Available from https://www.shopvgs.com/yes-card. Accessed 21 September 2017
51.
Family Fresh Market
.
PDFs of free medications available and of $4 or $10 medications available [Internet]
.
Available from https://www.familyfreshmarket.com/yes-card. Accessed 21 September 2017
52.
Walmart
.
Retail prescription program drug list [Internet]
.
Available from http://i.walmart.com/i/if/hmp/fusion/genericdruglist.pdf. Accessed 21 September 2017
53.
Target
.
$4 and $10 generic medication list [Internet]
.
54.
Torrey
T
.
Stores that offer free and low-cost prescription drugs: save money on your medications
.
55.
Kinmonth
AL
,
Woodcock
A
,
Griffin
S
,
Spiegal
N
,
Campbell
MJ
.
Randomised controlled trial of patient centred care of diabetes in general practice: impact on current wellbeing and future disease risk
.
BMJ
1998
;
317
:
1202
1208