Om P. Ganda, MD, Chair, Clinical Oversight Committee

The objective of the Joslin Diabetes Center Clinical Guideline for Pharmacological Management of Adults with Type 2 Diabetes is to support clinical practice, influence clinical behavior to improve outcomes, and to assure quality of care according to accepted standards. The guideline was established after careful review of current evidence, literature, and clinical practice. This guideline is reviewed periodically and modified to reflect changes in clinical practice and available pharmacological information. 

5.1.0 DIABETES MELLITUS: DIAGNOSTIC CRITERIA (NONPREGNANT ADULTS)

This guideline is not intended to serve as a mandatory standard, but rather to provide a set of recommendations for patient care management. These recommendations are not a substitute for sound and reasonable clinical judgment or decision making and do not exclude other options. Clinical care must be individualized to the specific needs of each patient and interventions must be tailored accordingly. The guideline has been created to address initial presentations and treatment strategies in the adult nonpregnant patient population. The guideline is not a substitution for full prescribing information. Refer to Joslin’s Clinical Guideline for Adults with Diabetes (Chapter 1) as well as Joslin’s Guideline for the Care of Older Adults With Diabetes (Chapter 4) for additional, more comprehensive information on diabetes care and management.

Random plasma glucose (PG) ≥200 mg/dl and symptoms of diabetes (polyuria, polydipsia, ketoacidosis, or unexplained weight loss) 

Results of a 2-hour 75-g oral glucose tolerance test ≥200 mg/dL at 2 hours

Only an A1C test that has been referenced to an accepted laboratory method (standardized) should be utilized for diagnostic purposes. Consider evaluation for hemoglobin variant if A1C is discordant from PG values.

5.2.0 GOALS OF GLYCEMIC CONTROL FOR INDIVIDUALS WITH DIABETES (

5.3.0 INITIAL TREATMENT STRATEGY (FIGURE)

5.3.1 Advancing antidiabetes medications:

These tests should be confirmed by a repeat test, on a different day, unless unequivocally high.

5.4.0 CONSIDERATIONS FOR SELECTING NONINSULIN GLUCOSE-LOWERING MEDICATIONS

5.4.1 First-line add-on to metformin or use as monotherapy if metformin is contraindicated: see table SP256

5.5.0 PREFERRED CONSIDERATIONS IN PATIENTS WITH T2D AND ESTABLISHED CARDIOVASCULAR DISEASE

 Preferred Considerations in Patients With T2D and Established Cardiovascular Disease

5.6.0 ORAL GLUCOSE-LOWERING MEDICATIONS (

5.6.1 Examples of fixed-dose medications: (Table 4)

5.7.0 INJECTABLE ANTIDIABETES MEDICATIONS (INCRETIN MIMETICS AND NONINSULIN ANALOGUES) (TABLE 5)

Considerations for Selecting Noninsulin Glucose-Lowering Medications

Goals should be individualized based on factors that include the following: comorbidities, age, duration of diabetes, hypoglycemic awareness.

If diet history reveals markedly excessive carbohydrate intake, consider initial trial of nutrition therapy and physical activity before initiating oral antidiabetes medications, even if glucose levels are above thethresholds listed.

Some patients with T2D initially stabilized on insulin may be considered for transition to noninsulin antidiabetes medications as blood glucose control permits.

May need to taper and discontinue some or all oral antidiabetes medications as insulin is initiated and adjusted, particularly if using short- or rapid-acting and basal insulins.

Pre- and postprandial blood glucose should be checked. Frequency of checking may vary; it can be 1 to 4 times/day depending on individual patient and status of glycemic control.

There is an increased risk for edema when insulin and a thiazoli-dinedione are used together. Rosiglitazone should not be used in combination with insulin.

FDA requirements for LFT monitoring for thiazolidinediones (TZDs): If initial alanine aminotransferase (ALT) is >2.5 times normal, do not start this medication. If ALT is >2.5 times normal during treatment, check weekly. If rise persists or becomes >3 times normal, discontinue TZD.

Thiazolidinediones cause or exacerbate congestive heart failure in some patients. After initiation of TZDs and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive or rapid weight gain; dyspnea; and/or edema). If these signs and symptoms develop, the heart failure should be managed according to current standards of care. Furthermore, discontinuation or dose reduction of the TZD must be considered. TZDs are not recommended in patients with symptomatic heart failure or in patients with established NYHA Class III or IV heart failure.

a. On September 23, 2010, the FDA announced regulatory actions with respect to products containing rosiglitazone: Avandia (rosiglitazone maleate) tablets, Avandamet (rosiglitazone maleate and metformin hydrochloride) tablets, and Avandaryl (rosiglitazone maleate and glimepiride) tablets. These FDA actions required GlaxoSmithKline to implement restrictions on the use of these products through a Risk Evaluation and Mitigation Strategy (REMS) program to assure their safe use and through additional safety labeling changes in responseto the agency’s review of data that suggested an elevated risk ofcardiovascular events. However, based on additional data review, the REMS program was removed as of December 16, 2015. Rosiglitazone now has the same indications for prescribing as pioglitazone.

9.b. According to the FDA advisory issued on June 15, 2011, regarding potential increased risk of bladder cancer with pioglitazone use: (1) Do not use pioglitazone in patients with active bladder cancer. (2) Use pioglitazone with caution in patients with a prior history of bladder cancer. The benefits of glycemic control versus unknown risks for cancer recurrence with pioglitazone should be considered in patients with a prior history of bladder cancer.

10. Risks of acute pancreatitis or pancreatic cancer have not been confirmed in clinical trials. The FDA is currently monitoring clinical reports via the Adverse Event Reporting System.

11. Diabetic ketoacidosis (DKA) with SGLT-2 inhibitors: Rare but sometimes serious cases have been reported. Check for DKA if symptomsdevelop, even if glucose levels are not elevated.

12. The potential benefits of SGLT-2 inhibitors in preventing progression of early renal disease are being investigated. 

1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. 

. 2011;34(suppl 1):S62-S69. doi: 10.2337/dc11-S062. 

2. Nathan DM, Kuenen J, Borg R, Zheung H, Schoenfield D, Heine RJ; A1c-Derived Aver- age Glucose Study Group. Translating the A1C assay into estimated average glucose values. 

. 2008;31(8):1473-1478. doi: 10.2337/dc08-0545.

Goals Of Glycemic Control And Pharmacotherapy

3. American Diabetes Association. 8. Pharmacological approaches to glycemic treatment: Standards of Medical Care in Diabetes—2018. 

. 2018;41(suppl 1):S73-S85. doi: 10.2337/dc18-S008.

4. Qaseem A, Wilt TJ, Kansagara D, Horwitch C, Barry MJ, Forciea MA; Clinical Guidelines Committee of the American College of Physicians. Hemoglobin A1c targets for glycemic control with pharmacologic therapy for nonpregnant adults with type 2 diabetes mellitus: a guidance statement update from the American College of Physicians. 

. 2018;168(8):569-576. doi: 10.7326/M17-0939.

5. Beaser RS, Staff of Joslin Diabetes Center. Joslin’s Diabetes Deskbook: A Guide for Primary Care Providers. 3rd ed. Boston, MA: Joslin Diabetes Center; 2014.

6. Massachusetts Department of Public Health’s Diabetes Prevention and Control Program. Massachusetts guidelines for adult diabetes care. Boston, MA: Massachusetts Department of Public Health; 2011.

7. Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm — 2018 executive sum- mary. Endocr Pract. 2018;24(1):91-120.

8. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. 

9. Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. 

10. DeFronzo RA, Eldor RE, Abdul-Ghani M. Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes. 

. 2013;36(suppl 2):S127- S138. doi: 10.2337/dcS13-2011.

11. Kahn SE, Haffner SM, Heise MA, et al; ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy [published correction appears in 

. 2006;355(23):2427-2443. doi: 10.1056/NEJMoa066224.

12. Nathan DM, Buse JB, Davidson MB, et al; American Diabetes Association; European Association for the Study of Diabetes. Medical management of hyperglycemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. 

. 2009;32(1):193-203. doi: 10.2337/dc08-9025.

13. Currie CC, Poole CD, Evans M, Peters JR, Morgan CL. Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes. 

. 2013;98(2):668-677.doi: 10.1210/jc.2012-3042.

14. Garvey WT. Use of available glucose-lowering agents in patients with different levels of renal impairment. 

. 2013;19(suppl 1):14-18. doi: 10.4158/EP12362.OR.

15. Berkowitz SA, Krumme AA, Avorn J, et al. Initial choice of oral glucose-lowering medication for diabetes mellitus: a patient-centered comparative effectiveness study.

. 2014;174(12):1955-1962. doi:10.1001/jamainternmed.2014.5294.

16. Bailey CJ. Interpreting adverse signals in diabetes drug development programs.

. 2013;36(7):2098-2106. doi: 10.2337/dc13-0182.

17. Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. 

. 2016;164(11):740-751. doi:10.7326/M15-2650.

18. Cryer DR, Nicholas SP, Henry DH, Mills DJ, Stadel BV. Comparative outcomes study of metformin intervention versus conventional approach: the COSMIC Approach Study. 

29. Grant PJ. The effects of high- and medium-dose metformin therapy on cardiovascular risk factors in patients with type II diabetes. 

20. Inzucchi SE. Metformin and heart failure: innocent until proven guilty.

.2005;28(10):2585-2587. doi: 10.2337/diacare.28.10.2585.

21. Johansen K. Efficacy of metformin in the treatment of NIDDM. meta-analysis.

22. Eppenga WL, Lalmohamed A, Geerts AF, et al. Risk of lactic acidosis or elevated lactate concentrations in metformin users with renal impairment: a population-based cohort study. 

. 2014;37(8):2218-2224. doi:10.2337/dc13-3023.

23. UK Prospective Diabetes Study (UKPDS 34) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) [published correction appears in Lancet. 1998;352(9139):1558]. 

24. Salpeter SR, Greyber E, Pasternak GA, Salpeter Posthumous EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus [update in Cochrane Database Syst Rev. 2010;(4):CD002967]. Cochrane 

.2010;(1):CD002967. doi: 10.1002/14651858.CD002967.pub3.

25. Phung OJ, Scholle JM, Talwar M, Coleman CI. Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes. 

. 2010;303(14):1410-1418. doi: 10.1001/jama.2010.405.

26. Stevens RJ, Ali R, Bankhead CR, et al. Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomized clinical trials. 

. 2012;55(10):2593-2603. doi: 10.1007/ s00125-012-2653-7.

27. Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK. Metformin in patients with type 2 diabetes and kidney disease: a systematic review.

. 2014;312(24):2668- 2675. doi: 10.1001/jama.2014.15298.

28. Charbonnel B, Roden M, Urquhart R, et al. Pioglitazone elicits long-term improvements in insulin sensitivity in patients with type 2 diabetes: comparisons with gliclazide-based regimens. 

29. Davidson JA, Perez A, Zhang J; the Pioglitazone 343 Study Group. Addition of piogli- tazone to stable insulin therapy in patients with poorly controlled type 2 diabetes: results of a double-blind, multicentre, randomized study. 

30. Mazzone T, Meyer PM, Feinstein SB, et al. Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: a randomized trial.

31. Yki-Jarvinen H. Thiazolidinediones. N Engl J Med. 2004;351(11):1106-1118.

32. Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes [published correction appears in N Engl J Med. 2007;357(1):100]. 

. 2007;356(24):2457-2471. doi: 10.1056/NEJMoa072761.

33. Dormandy JA, Charbonnel B, Eckland DJ, et al; PROactive Investigators. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial in macroVascular Events): a randomised controlled trial. 

34. Home PD, Pocock SJ, Beck-Nielsen H, et al; RECORD Study Team. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomized, open-label trial. 

. 2009;373(9493):2125-2135. doi: 10.1016/S0140-6736(09)60953-3.

35. Piccinni C, Motola D, Marchesini G, Poluzzi E. Assessing the association of pioglitazone use and bladder cancer through drug adverse event reporting.

.2011;34(6):1369-1371. doi: 10.2337/dc10-2412.

36. FDA Drug Safety Communication: FDA eliminates the Risk Evaluation and Mitigation Strategy (REMS) for rosiglitazone-containing diabetes medicines. FDA website. fda. gov/downloads/drugs/drugsafety/ucm477575.pdf. Updated December 16, 2015. Accessed December 16, 2015.

37. Lewis JD, Habel LA, Quesenberry CP, et al. Pioglitazone use and risk of bladder cancer and other common cancers in persons with diabetes. 

. 2015;314(3):265-277. doi: 10.1001/jama.2015.7996.

Articles

From the Adult Diabetes and Clinical Research Sections, Joslin Diabetes Center, Harvard Medical School. Approved May 10, 2016; updated April 24, 2018.

For the Figure and Tables, download the PDF at the end of the chapter.

CHAPTER 5. Clinical Guideline for Pharmacological Management of Adults With Type 2 Diabetes

The Joslin Guideline for the Care of the Older Adult with Diabetes is designed to assist primary care physicians, specialists, and other healthcare providers in addressing the unique challenges and issues of the older person with diabetes. The guideline should be used in conjunction with Joslin’s Clinical Guideline for Adults with Diabetes as well as Joslin’s Clinical Guideline for Pharmacological Management of Adults with Type 2 Diabetes (T2D).

The primary goal of diabetes management in older adults is to achieve balance between optimal glycemic control to prevent and/or slow the onset and progression of acute and chronic complications, while avoiding hypoglycemia and its consequences. Hypoglycemia can result in worse outcomes in older adults as it can lead to traumatic falls and worsening of chronic conditions such as cognitive dysfunction. Therefore, in many cases, aggressive treatment may not be appropriate if the older adult’s comfort, safety, and overall quality of life are thereby compromised, or if aggressive treatment may not improve outcomes. Recent consensus on the management of diabetes recommends individualization of treatment goals based on coexisting medical conditions, cognitive status, functionality, and available resources. The older adult’s view on illness, health, and aging should also be considered. Appropriate support systems for complex diabetes are not uniformly available nationwide. As a result, treatment decisions become more complex as the capacity to cope with self-care declines.

To assist with self-care, education strategies also require adaptation for aging. Learning new diabetes self-management skills may be difficult for older people, increasing the need for education to proceed in a simple, step-like manner. Cognitive dysfunction, depression, and functional disabilities (such as vision and hearing deficits and a decline in dexterity) are important issues to consider when assessing the older adult’s ability for self-care. Involvement of family members or friends may be required to assure appropriate self-care and adherence to treatment programs.

Portions of this guideline are based upon recommendations of the International Diabetes Federation’s Global Guideline for Managing Older People with Type 2 Diabetes and the American Diabetes Association/American Geriatrics Society Consensus Report on Diabetes in Older Adults.

In determining treatment plans and goals, individualized patient assessment is required, being cognizant of the following:	

Chronological age versus actual health status

Duration of disease and age of onset (for example, older-age onset of T2D is more prominent in non-Hispanic whites and is associated with a lower likelihood of insulin use than middle-age onset; retinopathy is more likely to occur in middle-age—onset diabetes rather than older-age–onset diabetes. There is no difference in coronary artery disease or neuropathy prevalence in middle vs older age onset)

Presence of complications and comorbidities 

Treatment programs should be simplified to decrease the potential of medication errors and to avoid overwhelming the patient and their caregivers.

Treatment goals should be reassessed at frequent intervals as health status can change quickly in older adults.

The table in this guideline (Table 1) lists a group of conditions collectively called geriatric syndrome, which occurs more frequently in older adults with diabetes. These conditions can interfere with a patient’s ability to perform self-care activities and make healthcare more challenging for the older adult and for their caregivers. The table below includes the condition, possible clinical presentations, commonly used short clinical screening tests, and suggested modifications to treatment plans and goals to compensate for the condition.

See Joslin’s Clinical Guideline for Adults with Diabetes (Chapter 1) for more details.

CDC data indicate that about half of older adults have prediabetes. It is recommended that all adults >45 years of age be screened for diabetes every 1 to 3 years using a glycated hemoglobin (A1C), fasting glucose, or oral glucose tolerance test. This recommendation should be modified for those with shorter life expectancies and those with multiple comorbidities.

See Joslin’s Clinical Guideline for Adults with Diabetes for more details. Treatment goals are modified for health status, based on recommendations from the American Diabetes Association.

Treatment goals for A1C, glucose, blood pressure, and lipid levels should be modified for the older adult based on patient characteristics and on health status. See Table 2 below.

Education strategies require adaptation for aging. Simplify and focus programs:

Use focused educational material that is easy to follow and excludes extraneous information.

Provide individual rather than group education if the patient has cognitive or physical deficits.

Focus on 1 to 2 topics at a time. Repetition and re-education are needed for many older adults.

Education sessions should be slow-paced, with instruction occurring in steps.

Multiple sessions may need to be scheduled, to prevent “information overload.”

Use memory aids (eg, personalized handouts) to reinforce points made during face-to-face sessions.

When possible, simplify the patient’s medication program especially for those who have multiple medical problems, cognitive dysfunction, or functional disability (eg, changing insulin to 2 injections per day from 4 injections per day).

When discussing medications, focus education on medication adherence by using charts, pill boxes, and other reminders.

Caregivers should be instructed in how to track amounts of medication used.

Educate the patient that uncommon symptoms such as confusion, dizziness, and weakness can be manifestations of hypoglycemia.

Involve the patient’s caregiver or arrange for visiting nurse evaluation if medication adherence is an issue.

Provide very specific guidelines on when the patient and/or caregiver should call the healthcare provider for assistance.

Recommend equipment that is easy to hold, easy to read, and requires the least number of steps.

Insulin pens, pens that contain noninsulin glucose- lowering medication, and prefilled syringes may be easier for older patients to use than manipulating a syringe and vial. Syringe magnifiers are available if vision is impaired.

For some patients, inhaled insulin may be another option for prandial insulin.

Choose blood glucose meters that have a large display, are easy to hold and use, and that minimize handling of strips and lancets. “Talking meters” are available for those with vision impairment.

Emphasize the importance of regular self-monitoring of blood glucose (SMBG), especially before driving or using power tools.

Checking glucose levels at different times of the day, on different days of the week, will allow the provider to assess glucose patterns throughout the day without having the patient check the glucose several times each day. For example, check the fasting and presupper glucose levels one day, and prelunch and bedtime levels another day.

Some older adults may not be able to perform SMBG due to physical or cognitive impairment. To decrease the risk of hypoglycemia in these situations, glycemic goals may need to be adjusted and medication programs may need to be simplified. In T2D, if appropriate, use diabetes medications that have a low risk for hypoglycemia.

Develop a plan to treat hypoglycemia. Encourage the patient to carry a source of glucose on their person and to have one at the bedside at all times.

Encourage caregivers to accompany patients to education sessions and receive appropriate education in glucose monitoring and blood glucose interpretation.

A referral for education and counseling should be advised if the patient’s ability to drive is in question. Organizations such as local elder services, the American Geriatric Society, and the various state motor vehicle registries may have additional information for patients as well as family members.

Drive-wise programs, where available, can be useful to assess the patient’s ability to drive.

4.9.0 NUTRITION CHALLENGES (see Appendix for examples of nutrition prescriptions)

Although diabetes nutritional guidelines for the older adult are no different than for younger adults, unique challenges often exist due to:

Impaired food shopping or preparation capabilities

Omission of meals due to cognitive dysfunction or depression

Consider referral to a dietitian to work with the older adult patient and caregivers to: 

Avoid making unnecessary dietary changes in life-long eating habits, remembering that to treat coexisting illnesses multiple changes may be required, such as reducing potassium, sodium, and dietary fats

Minimize the complexity of meal planning and engage the spouse, or others living with the patient, in creating a home environment that supports positive lifestyle change

Educate how consistency in carbohydrate intake and meal timing can help minimize fluctuations in blood glucose levels as well as help maintain or achieve a reasonable weight

Consider giving prandial insulin after the meal rather than before, based on carbohydrate intake

Assess the ability to buy and prepare healthy meals

Suggest community resources such as Meals on Wheels

4.9.2 Weight loss/potential malnutrition:

Weight-loss diets commonly recommended to younger adults should be prescribed with great caution to the older adult, since undernutrition/malnutrition is often more of a problem than obesity in the older adult.

Weight loss and the potential for malnutrition should be carefully monitored, especially after acute illness, hospitalization, and social stress.	

Use serial weight measurements to monitor changes.

To avoid weight loss, it may be necessary to let patients eat what they enjoy and adjust diabetes medications accordingly.

In chronic care settings, there is no need for a rigid and restrictive meal plan. A regular meal plan with consistent, moderate carbohydrate intake may be sufficient and may help avoid undernutrition. 

(see Appendix for examples of activity prescriptions)

Physical activity should be stressed in all older adults as it is crucial in maintaining functionality, independence, and acceptable quality of life.

Regular exercise program offers other benefits to older adults, such as: 	

Decreased depression, and an overall sense of improved well-being.

Types of physical activities that may be appropriate for the older adult should take into account the current level of physical fitness/disability. It is important to develop an activity program to increase mobility, endurance, and strength, and to increase the duration of the activity gradually. Common activities to achieve these goals include:	

Challenges to maintaining a regular physical activity program include:	

Comorbidities, such as cardiovascular disease, osteoarthritis, and osteoporosis

The risk of hypoglycemia is increased among those using insulin and other diabetes medications that can cause hypoglycemia. More frequent SMBG may reduce this risk

An exercise physiologist or a physical or occupational therapist can provide a supervised environment to help a patient perform exercises safely.

4.11.0 MEDICATIONS: GENERAL CONSIDERATIONS

General principles to consider when prescribing medications to an older adult include:

“Start low and go slow” when dosing and titrating medications

Agents with low risk of hypoglycemia are preferred in this age group

Deintensification (or simplification) of complex regimens is recommended to reduce the risk of hypoglycemia

is common in older adults and should be avoided.

Consider drug—drug interactions carefully, as most older adults are on multiple medications as well as supplements

Evaluate renal function using the estimated glomerular filtration rate (eGFR) rather than serum creatinine because low muscle mass in the older population may result in a “normal” creatinine level despite significant renal dysfunction

Monitor liver and kidney function with periodic tests

Assess financial resources when using newer, generally more expensive agents

From the Adult Diabetes and Clinical Research sections, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts.

This guideline was revised and approved May 17, 2017, and updated February 7, 2018.

CHAPTER 4. Guideline for the Care of the Older Adult With Diabetes

The Joslin Guideline for Detection and Management of Diabetes in Pregnancy is designed to assist internal medicine specialists, endocrinologists, and obstetricians in individualizing the care of and setting goals for women with preexisting diabetes who are pregnant or planning pregnancy. It is also a guide for managing women who are at risk for or who develop gestational diabetes mellitus (GDM). This guideline is not intended to replace sound medical judgment or clinical decision making. Clinical judgment determines the need for adaptation in all patient care situations; more or less stringent interventions may be necessary.

3.1.0 SCREENING FOR GESTATIONAL DIABETES MELLITUS

3.2.0 PRECONCEPTION CARE. For preexisting type 1 diabetes (T1D) or type 2 diabetes (T2D)

The objective of the Joslin Guideline for Detection and Management of Diabetes in Pregnancy is to support clinical practice and to influence clinical behaviors in order to improve clinical outcomes and assure that patient expecta- tions are reasonable and informed. This guideline was approved November 13, 2016, and updated February 12, 2018.

See at end of Chapter 3 (download PDF at end of chapter).

Fasting and pre-meal glucose: plasma 80 to 110 mg/dL [1C]

1-hour postprandial blood glucose: plasma 100 to 155 mg/dL [1C]

Glycated hemoglobin (A1C): <7% and as close to 6% as possible, without severe hypoglycemia [1B]

Educate women of childbearing age about the importance of near-normal blood glucose control prior to conception.

Refer to a specialist in maternal—fetal medicine and/ or endocrinology/diabetes for counseling, assessment of maternal and fetal risk, and guidance in achieving management goals. This includes all women who are planning pregnancy and women who are not planning pregnancy but are using inadequate contraception and have A1C greater than 7%.

Assess diabetes self-management, including meal planning, insulin care and use, activity program, medication schedule, self-monitoring of blood glucose (SMBG), treatment for hypoglycemia and hyperglycemia, and sick day management, utilizing diabetes educators (DEs) as appropriate. Review maternal and fetal health issues.

Begin a multivitamin with 400 mcg of folic acid to supplement average daily intake of 400 mcg for a total daily intake of 800 mcg to 1 mg of folic acid to decrease the risk of neural tube defects. Patients with a prior pregnancy affected with a neural tube defect should take folic acid 4 mg daily.

Strongly advise smoking and alcohol cessation.

Refer overweight and obese women with and without known diabetes or polycystic ovary syndrome (PCOS) for medical nutrition therapy with a goal of 5% to 10% weight loss based on 2009 Institute of Medicine recommendation

Take thorough medical and obstetrical history, including comprehensive review of diabetes history and management.

Eye evaluation: dilated comprehensive eye exam and pregnancy clearance by an ophthalmologist; should also include a discussion about the risk of developing and/or the progression of diabetic retinopathy during pregnancy.

Kidney function assessment: random urine albumin/ creatinine ratio and serum creatinine. Refer to nephrology if urine protein >1 gram.

Thyroid evaluation: Check thyroid stimulating hormone level.

Gynecology evaluation: Make sure pelvic exam and Pap smear are up to date.

Cardiac evaluation: If asymptomatic and ≥ 35 years of age with 1 or more additional risk factors (hypertension, smoking, family history of coronary artery disease, hypercholesterolemia, albuminuria, or nephropathy), recommend 1 or more of the following: electrocardio- gram (ECG), echocardiogram, or exercise tolerance test (ETT). If symptomatic, recommend ECG and echocar- diogram or ETT and consider referral to cardiologist.

Check vitamin B12 level in patients consuming more than 1 mg folic acid daily, as high-dose folic acid may mask a B12 deficiency.

Discontinue oral antihyperglycemic therapy; start insulin. An exception is metformin, which may be continued during anovulatory infertility and in the first trimester in patients with PCOS or T2D. Prior

	to the first prenatal visit, the patient should begin increasing doses of insulin as necessary to control blood glucose while metformin is tapered off or discontinued. Metformin should not be used beyond the first trimester or in lieu of insulin based on safety and efficacy data available at this time. 	

Metformin crosses the placenta and achieves therapeutic levels in the fetus. Presently, there are no long term randomized controlled trials (RCT) regarding outcomes in offspring of mothers with preexisting diabetes treated with metformin during pregnancy. (See 3.3.3b regarding outcomes in infants exposed to metformin in utero in PCOS and GDM.).

Other oral medications have not been adequately studied for the treatment of preexisting T2D in pregnancy.

The rapid-acting insulin analogs lispro and aspart lower postprandial blood glucose and decrease the risk of nocturnal hypoglycemia. Patients on lispro and aspart prior to conception may continue them during pregnancy. Patients on regular insulin may be switched to lispro or aspart if 1-hour postprandial blood glucose levels are above target and/or the patient is also experiencing pre-meal or nocturnal hypoglycemia.

No information exists on the safety of using the insulin analogs glulisine and degludec in pregnancy. We cannot recommend their use at this time.

A rapid-acting insulin, lispro or aspart, may be delivered either through multiple daily injections or an insulin pump.

Detemir is a long-acting insulin analog that has been studied in T1D and is noninferior to isophane insulin in terms of safety, efficacy, and outcomes.

From the Adult Diabetes and Clinical Research sections, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts

Om P. Ganda, MD, Chair, Clinical Oversight Committee

Articles

CHAPTER 5. Clinical Guideline for Pharmacological Management of Adults With Type 2 Diabetes

CHAPTER 4. Guideline for the Care of the Older Adult With Diabetes

CHAPTER 3. Guideline for Detection and Management of Diabetes in Pregnancy

CHAPTER 2. Clinical Nutrition Guideline for Overweight and Obese Adults With Type 2 Diabetes (T2D) or Prediabetes, or Those at High Risk for Developing T2D

CHAPTER 1. Clinical Guideline for Adults With Diabetes