INTRODUCTION — Diabetes mellitus is a common disorder, affecting nearly half a billion people worldwide and 8 to 9 percent of the population in the United States.
●(See "Type 2 diabetes mellitus: Prevalence and risk factors", section on 'Prevalence'.)
Hypertension occurs frequently in patients with diabetes and, together, diabetes and hypertension substantially increase the risk of cardiovascular and kidney disease. Effective treatment of hypertension in such patients reduces cardiovascular risk. (See "Overview of established risk factors for cardiovascular disease".) (Related Pathway(s): Hypertension: Initial management.)
The pathogenesis, epidemiology, and choice of antihypertensive therapy in patients with diabetes mellitus are presented in this topic. The diagnosis of hypertension and goal blood pressure in patients with diabetes are discussed separately:
●(See "Blood pressure measurement in the diagnosis and management of hypertension in adults".)
●(See "Goal blood pressure in adults with hypertension", section on 'Patients with diabetes mellitus'.)
PATHOGENESIS — In addition to the development of kidney disease, at least two other factors have been proposed to contribute to hypertension in diabetes: extracellular fluid volume expansion and increased arterial stiffness [1].
Sodium retention and volume expansion may be induced both by insulin and the hyperglycemia-induced increase in the filtered glucose load [2,3]. The excess filtered glucose is reabsorbed in the proximal tubule via a sodium-glucose cotransporter, resulting in a parallel rise in sodium reabsorption [3]. Thus, salt loading tends to raise the blood pressure, an effect that can be reversed by salt restriction.
Patients with diabetes have increased vascular stiffness [1], which is thought to be a consequence of increased protein glycation and, at a later stage, atheromatous disease. The reduction in arterial distensibility, which is seen with both impaired glucose tolerance and overt diabetes, can contribute to the rise in systolic pressure disproportionately to diastolic pressure and is associated with increased blood pressure variability and mortality risk [4,5].
EPIDEMIOLOGY — Hypertension is a common problem in patients with both type 1 and type 2 diabetes, but the time course in relation to the duration of diabetes is different [2,6-9].
Among those with type 1 diabetes, the incidence of hypertension rises from 5 percent at 10 years, to 33 percent at 20 years, and to 70 percent at 40 years [2]. There is a close relation between the prevalence of hypertension and increasing albuminuria. The blood pressure typically begins to rise within the normal range at or within a few years after the onset of moderately increased albuminuria (the new term for what was previously called "microalbuminuria" and what is also sometimes called "high albuminuria") [7]. Blood pressure then increases progressively as the kidney disease progresses. (See "Moderately increased albuminuria (microalbuminuria) in type 1 diabetes mellitus", section on 'Risk factors'.)
These features were illustrated in a study of 981 patients who had type 1 diabetes for five or more years [8]. Hypertension was present in 19 percent of patients with normoalbuminuria, 30 percent with moderately increased albuminuria, and 65 percent with severely increased albuminuria (the new term for what was previously called "macroalbuminuria" and what is sometimes called "very high albuminuria") [7]. The incidence of hypertension eventually reaches 75 to 85 percent in patients with progressive diabetic nephropathy [10]. The risk of hypertension is highest in Black individuals, who are also at much greater risk for kidney failure due to diabetic kidney disease. (See "Diabetic kidney disease: Pathogenesis and epidemiology".)
The findings are different in patients with type 2 diabetes [11-13]. In a series of over 3500 newly diagnosed patients, 39 percent were already hypertensive [11]. In approximately one-half of these patients, the elevation in blood pressure occurred before the onset of moderately increased albuminuria. Hypertension was strongly associated with obesity, and not surprisingly, the hypertensive patients were at increased risk for cardiovascular morbidity and mortality. Among patients with diabetes in general (regardless of vintage) in the United States, the prevalence of hypertension is nearly 70 percent. (See "Moderately increased albuminuria (microalbuminuria) in type 2 diabetes mellitus".)
GOAL BLOOD PRESSURE — UpToDate recommendations on goal blood pressure in hypertensive patients with diabetes mellitus are presented in detail elsewhere. In general, patients with diabetes are at higher cardiovascular risk compared with the general population, and therefore we suggest more intensive, rather than less intensive, blood pressure control. (See "Goal blood pressure in adults with hypertension", section on 'Patients with diabetes mellitus'.)
Goal blood pressure also depends upon the method by which it is measured (table 1). (See "Goal blood pressure in adults with hypertension", section on 'Importance of how blood pressure is measured'.)
Our recommendations are broadly consistent with the 2017 American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines [14], as well as the American Diabetes Association (ADA) guidelines that suggest a goal blood pressure of less than 130/80 mmHg in patients with diabetes mellitus who have greater than a 10 percent 10-year cardiovascular risk [15,16].
Support for these recommendations comes from randomized trials, meta-analyses, and large observational studies [17-20]. A detailed presentation of the rationale for our approach, including a discussion of the Action to Control Cardiovascular Risk in Diabetes blood pressure trial (ACCORD BP) [21], is found in a separate topic. (See "Goal blood pressure in adults with hypertension", section on 'Patients with diabetes mellitus'.)
APPROACH TO LOWERING BLOOD PRESSURE — Since hypertension magnifies cardiovascular risk among those with diabetes, all patients with diabetes and persistently elevated blood pressure should be started on antihypertensive drug therapy [16,22-25]. Drug therapy in patients with diabetes and hypertension is unequivocally protective [17,26-32]. (See 'Choice of antihypertensive drug therapy' below.)
In addition, all patients with diabetes and elevated blood pressure should be counseled on lifestyle modification to reduce blood pressure. Successful implementation of nonpharmacologic therapy may permit later reduction in the dose or number of antihypertensive agents. (See 'Nonpharmacologic therapy (lifestyle modification)' below and "Can drug therapy be discontinued in well-controlled hypertension?".)
Nonpharmacologic therapy (lifestyle modification) — Nonpharmacologic interventions to prevent and treat hypertension include lifestyle modifications such as (table 2):
●Salt restriction (see "Salt intake, salt restriction, and primary (essential) hypertension")
●Weight reduction (see "Overweight, obesity, and weight reduction in hypertension")
●Increased consumption of fresh fruits, vegetables, and low-fat dairy products (see "Diet in the treatment and prevention of hypertension")
●Increased exercise (see "Exercise in the treatment and prevention of hypertension")
●Avoidance of smoking and excess alcohol ingestion (see "Smoking and hypertension" and "Overview of hypertension in adults", section on 'Nonpharmacologic therapy')
We agree with the American Diabetes Association (ADA) 2020 guidelines, which advise that, among patients with a systolic blood pressure ≥120 mmHg or a diastolic pressure ≥80 mmHg, such nonpharmacologic methods should be used to reduce blood pressure [33].
When to initiate antihypertensive drug therapy — The decision to initiate drug therapy should be individualized and involve shared decision-making between patient and provider. In general, however, we suggest that antihypertensive drug therapy be initiated in the following hypertensive patients (our suggestions broadly agree with those recommendations made by the 2017 American College of Cardiology/American Heart Association [ACC/AHA] guidelines and by the 2020 ADA guidelines) [14,15,33] (see "Overview of hypertension in adults", section on 'Who should be treated with pharmacologic therapy?'):
●Patients with out-of-office daytime blood pressure ≥135 mmHg systolic or ≥85 mmHg diastolic (or an average office blood pressure ≥140/90 mmHg if out-of-office readings are not available)
●Patients with an out-of-office daytime blood pressure ≥130 mmHg systolic or ≥80 mmHg diastolic (or an average of appropriately measured office blood pressures ≥130/80 mmHg if out-of-office readings are not available) who, in addition, have one or more of the following:
•Established clinical cardiovascular disease (eg, chronic coronary syndrome [stable ischemic heart disease], heart failure, carotid disease, previous stroke, or peripheral arterial disease)
•Type 2 diabetes mellitus
•Chronic kidney disease
•Age 65 years or older
•An estimated 10-year risk of atherosclerotic cardiovascular disease of at least 10 percent (calculator 1)
These recommendations differ slightly from the 2020 ADA guidelines; specifically, the ADA suggests not starting antihypertensive drug therapy in a patient with type 2 diabetes and blood pressure <140/<90 mmHg if the predicted 10-year risk is <10 percent.
Early treatment of hypertension is particularly important in patients with diabetes both to prevent cardiovascular disease and to minimize progression of kidney disease and diabetic retinopathy [34]. This is exemplified by the 21-year follow-up of the Steno diabetes study; specifically, appropriate management of systolic blood pressure, glycated hemoglobin (A1C), and low-density lipid (LDL) cholesterol resulted in a 20 percent absolute risk reduction at 13 years, a benefit that was persistent at 21 years [35,36].
Choice of antihypertensive drug therapy — The choice of antihypertensive agents in patients with diabetes is based upon their ability to do the following:
●Prevent mortality
●Prevent adverse cardiovascular events, such as myocardial infarction, stroke, and heart failure
●Prevent the progression of kidney disease, if present
The choice is not based upon retinopathy endpoints, since comparative trials have not demonstrated superiority of one agent over another for retinopathy. (See "Diabetic retinopathy: Prevention and treatment", section on 'Good blood pressure control'.)
Overview of our approach — Major guidelines including the 2017 ACC/AHA, European Society of Hypertension/European Society of Cardiology (ESH/ESC), ADA, and Canadian guidelines all conclude that the degree of blood pressure reduction is the major determinant of reduction in cardiovascular risk in both younger and older patients with hypertension (including patients with diabetes), not the choice of antihypertensive drug; this is also true in patients with diabetes [37]. (See "Choice of drug therapy in primary (essential) hypertension".)
However, in patients with diabetic kidney disease, renin-angiotensin system inhibitors (angiotensin-converting enzyme [ACE] inhibitors or angiotensin receptor blockers [ARBs]) may slow kidney disease progression more effectively than other antihypertensive drugs. In addition to kidney disease, placebo-controlled trials of ACE inhibitors and ARBs in high-risk patients have led some experts to conclude that these agents have a unique cardiovascular benefit in this setting [38,39]. However, the available data are more consistent with the conclusion that the achieved blood pressure, rather than the specific drug or drug class used, is the principal determinant of cardiovascular benefit. (See "Choice of drug therapy in primary (essential) hypertension".)
Based upon the effects of ACE inhibitors and ARBs on kidney disease progression, our overall approach in patients with diabetes who require antihypertensive therapy is as follows:
●In patients with severely increased albuminuria, ≥300 mg/day (formerly called "macroalbuminuria" and sometimes called "very high albuminuria"), we treat with an ACE inhibitor or an ARB as part of the regimen to achieve the blood pressure goal. (See 'Severely increased albuminuria (300 mg/day or higher)' below.)
●We also use these drugs in patients with moderately increased albuminuria (formerly called "microalbuminuria" and sometimes called "high albuminuria") who are hypertensive, even though the benefits of angiotensin inhibition on kidney disease progression in such patients are unproven. (See 'Moderately increased albuminuria (30 to 299 mg/day)' below.)
●In patients without increased albuminuria, initial monotherapy can consist of an ACE inhibitor, ARB, thiazide diuretic, or calcium channel blocker. However, because thiazide diuretics have the disadvantage of an adverse effect on glucose metabolism, many experts will choose an ACE inhibitor, ARB, or calcium antagonist as initial therapy.
●In patients whose blood pressure is >20/10 mmHg above their goal, initial combination therapy (with a single pill, if available) should be prescribed. In addition, among patients with diabetes initiated on monotherapy, a second agent will often be required to attain goal blood pressure. In these settings (ie, when two antihypertensive drugs are needed), we generally treat with an ACE inhibitor or ARB plus a long-acting dihydropyridine calcium channel blocker. The combination of an ACE inhibitor or ARB with a diuretic is an acceptable alternative, and may be preferred in patients with edema; however, the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial suggested that combining an ACE inhibitor or ARB with a long-acting dihydropyridine calcium channel blocker was superior to the combination with a thiazide diuretic [40], including among patients with diabetes [41]. (See "Choice of drug therapy in primary (essential) hypertension".)
When using two antihypertensive medications, a single-pill combination is usually preferred since it is associated with better medication adherence. (See "Patient adherence and the treatment of hypertension", section on 'Methods to improve adherence'.)
If an ACE inhibitor or ARB is indicated but cannot be used, alternative first-line agents include calcium channel blockers and diuretics. However, in patients with severely increased albuminuria, nondihydropyridine agents (eg, diltiazem, verapamil) are generally preferred over dihydropyridine drugs (eg, amlodipine, felodipine) since nondihydropyridine calcium channel blockers can reduce albuminuria [42,43].
Major side effects of ACE inhibitors and ARBs are reviewed separately. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers".)
Severely increased albuminuria (300 mg/day or higher) — In hypertensive patients with diabetes who have severely increased albuminuria, defined as a measured (eg, with a 24-hour urine collection) or estimated (eg, using a random urine albumin-to-creatinine ratio [ACR]) albumin excretion ≥300 mg/day, we recommend treatment with an ACE inhibitor or an ARB rather than other antihypertensive agents. Other drugs can be added, as needed, to attain the blood pressure goal.
This approach is based upon high-quality, randomized trials demonstrating that these agents slow the progression of kidney disease compared with alternative therapy [44-47]. In addition, indirect evidence from trials of nondiabetic individuals supports the conclusion that ACE inhibitors and ARBs reduce the risk of kidney failure among those with severely increased albuminuria [48,49]. However, ACE inhibitors and ARBs do not appear to decrease all-cause mortality or the incidence of major cardiovascular events compared with other antihypertensive drugs.
●Type 1 diabetes – The best data supporting angiotensin inhibition in patients with type 1 diabetes come from a trial of 409 adult participants who had urine protein excretion ≥500 mg/day and a serum creatinine ≤2.5 mg/dL (221 micromol/L) [44,45]. Patients were randomly assigned to captopril (25 mg three-times daily) or placebo; other antihypertensive drugs, except for calcium channel blockers, were added if needed. Captopril reduced the rate of death or end-stage kidney disease (ESKD; 11 versus 21 percent) at three years, reduced the likelihood of doubling of serum creatinine (12 versus 21 percent), and slowed the annual loss of creatinine clearance (11 versus 17 percent per year). Smaller trials similarly concluded that ACE inhibitor slow the progression of kidney disease in patients with type 1 diabetes [50,51].
●Type 2 diabetes – In type 2 diabetes, the best data comparing renin-angiotensin system inhibition with alternative therapy come from the Irbesartan Diabetic Nephropathy Trial (IDNT) and the Reduction of Endpoints in Non-Insulin-Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) trial [46,47]:
•In IDNT, 1715 participants aged 30 to 70 years with type 2 diabetes, hypertension, urine protein excretion ≥0.9 g/day, and mean serum creatinine of 1.7 mg/dL (150 micromol/L) were randomly assigned to irbesartan (75 to 300 mg once daily), amlodipine (2.5 to 10 mg once daily), or placebo [46]. Target systolic blood pressure was ≤135 mmHg, or 10 mmHg lower than the value at screening (if systolic blood pressure at screening ≥145 mmHg), and target diastolic blood pressure was ≤85 mmHg. At 2.6 years, the likelihood of a doubling of serum creatinine was lower with irbesartan (17 percent) compared with amlodipine (25 percent) and placebo (24 percent); in addition, irbesartan nonsignificantly reduced the incidence of ESKD (14 versus 18 percent with amlodipine and placebo) (figure 1). Patients assigned to placebo had a higher blood pressure throughout the trial than those assigned irbesartan; however, the blood pressure in the irbesartan and amlodipine groups were similar, and therefore the benefits from irbesartan were independent of attained blood pressure [52,53].
•In RENAAL, 1513 adults with type 2 diabetes, albuminuria >300 mg/day (median urinary ACR of approximately 1250 mg/g), and mean serum creatinine 1.9 mg/dL (168 micromol/L) were randomly assigned to losartan (50 titrating up to 100 mg once daily) or placebo; additional drugs were added as need to attain goal blood pressure [47]. At 3.4 years, the incidence of ESKD was lower with losartan (20 versus 26 percent), as was doubling of serum creatinine (22 versus 26 percent). Unlike IDNT, there was no active comparator, and the mean blood pressure throughout the study was lower among those assigned losartan.
ACE inhibitors and ARBs have similar effects on patient-important outcomes among patients with diabetes as well as among broader populations [54-59]. Thus, in general, either agent can be used when treating patients with diabetes and albuminuria.
Some studies suggest that ACE inhibitors are superior to ARBs in preventing mortality and cardiovascular events in patients with diabetes. As an example, a meta-analysis of 48 trials that compared ACE inhibitors or ARBs with either placebo or another antihypertensive drug found that ACE inhibitors significantly reduced mortality compared with placebo (9.3 versus 10.5 percent) but that ARBs did not reduce mortality compared with placebo (5 versus 5 percent) [54]. However, both ACE inhibitors and ARBs had similar, nonsignificant benefits on mortality when compared with another antihypertensive drug (10.2 versus 11.9 percent and 8.5 versus 10.5 percent, respectively). The lack of benefit when ARBs were compared with placebo may be due to the fact that one-half of these trials included lower-risk patients (ie, normotensive and/or those with normoalbuminuria). In addition, both drugs had significant benefits on heart failure; ACE inhibitors significantly reduced the risk of myocardial infarction, and ARBs significantly reduced the risk of stroke.
Other meta-analyses that included many of the same trials found that, in contrast to the study mentioned above, ARBs are equivalent to ACE inhibitors. One network meta-analysis, for example, used both direct and indirect comparisons to evaluate trials of antihypertensive therapy in patients with diabetes and found that ACE inhibitors and ARBs had identical effects on mortality and ESKD [55]. In addition, a meta-analysis that included patients with and without diabetes found that ACE inhibitors and ARBs reduced mortality and cardiovascular events to a similar degree [56].
Moderately increased albuminuria (30 to 299 mg/day) — In hypertensive patients with diabetes who have moderately increased albuminuria, defined as a measured (eg, with a 24-hour urine collection) or estimated (eg, using a random urine ACR) albumin excretion 30 to 299 mg/day, we suggest treatment with an ACE inhibitor or ARB rather than other antihypertensive drugs. Additional agents are added, as needed, to attain the blood pressure goal.
The rationale for this approach comes from evidence that ACE inhibitors and ARBs, compared with other antihypertensive agents, can prevent the progression from moderately increased albuminuria to severely increased albuminuria in patients with diabetes [60-62]. In addition, these drugs may slow the rise in serum creatinine [63], and observational data suggest that a reduction in albuminuria is associated with a decreased incidence of ESKD [64].
However, there are no high-quality data that, in patients with moderately increased albuminuria, ACE inhibitors and ARBs are superior to other first-line agents in preventing kidney failure, all-cause mortality, or cardiovascular events.
Normoalbuminuria (less than 30 mg/day) — In patients without increased albuminuria (ie, measured or estimated albumin excretion <30 mg/day), initial monotherapy can consist of an ACE inhibitor, ARB, thiazide diuretic, or calcium channel blocker. However, because thiazide diuretics have the disadvantage of an adverse, albeit minor, effect on glucose metabolism, many experts will choose an ACE inhibitor, ARB, or a calcium antagonist as initial therapy. This approach is generally similar to the selection of antihypertensive therapy in patients without diabetes. (See "Choice of drug therapy in primary (essential) hypertension".)
In patients with diabetes and normoalbuminuria, ACE inhibitors and ARBs do not provide superior protection against ESKD, all-cause mortality, and cardiovascular events, compared with other first-line drugs [14].
Avoid combination renin-angiotensin system inhibition — A separate issue is whether an ARB should be given with an ACE inhibitor since combining these agents provides better blood pressure control compared with monotherapy and also reduces albuminuria to a greater degree [65]. However, based upon high-quality data in patients with diabetes as well as other individuals at high cardiovascular risk, we recommend against combination therapy with an ACE inhibitor and ARB or direct renin inhibitor [66].
In the subgroup analysis of the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) trial cited above, ramipril, telmisartan, and combination therapy were compared in 6365 patients with diabetes [58]. There was no difference in the composite primary outcome of death from cardiovascular causes, myocardial infarction, stroke, or hospitalization for heart failure among these groups. However, in the entire cohort, which comprised 25,620 patients with vascular disease or diabetes, there was an increase in adverse side effects (including a possible increase in mortality) in patients who received both agents, compared with those who received ramipril alone [58,59]. (See "Major side effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers".)
In addition, the combination of an ACE inhibitor with an ARB or with a direct renin inhibitor in two other large trials of patients with diabetic chronic kidney disease (Aliskiren Trial in Type 2 Diabetes Using Cardiovascular and Renal Disease Endpoints [ALTITUDE] and Veterans Affairs Nephropathy in Diabetes [VA NEPHRON-D]) was not superior to ACE inhibitor monotherapy and produced more side effects. (See "Treatment of diabetic kidney disease".)
A subsequent multiple-treatment comparison (network) meta-analysis suggested that combination therapy with an ACE inhibitor and ARB was superior to placebo in preventing ESKD in patients with diabetes and hypertension [67]. However, monotherapy with either an ACE inhibitor or an ARB produced similar benefits compared with placebo, and combination therapy produced more adverse effects.
INDICATIONS FOR ALTERNATIVE ANTIHYPERTENSIVE DRUGS — The choice of initial antihypertensive therapy may vary from the approach described above if the patient has one of the following disorders:
●A recent myocardial infarction (ie, in the previous three years) (see 'Patients with a recent myocardial infarction' below)
●Heart failure (see 'Patients with heart failure' below)
Patients with a recent myocardial infarction — Beta blockers, while generally not recommended as initial monotherapy or as part of combination therapy in patients with hypertension, are indicated in patients who have had a myocardial infarction in the previous three years. Patients who have had a myocardial infarction are also frequently prescribed an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB), regardless of whether they have albuminuria. (See "Acute myocardial infarction: Role of beta blocker therapy", section on 'Long-term therapy' and "Angiotensin converting enzyme inhibitors and receptor blockers in acute myocardial infarction: Recommendations for use".)
Although there are concerns about masking of hypoglycemic symptoms and possible exacerbation of peripheral artery disease, beta blockers can effectively lower blood pressure in patients with diabetes. Among beta blockers, carvedilol, a combined nonselective beta- and alpha-1 adrenergic antagonist that improves survival in patients with heart failure, may have certain advantages compared with other beta blockers in patients with diabetes [68,69]. However, bisoprolol and metoprolol extended release are reasonable alternatives.
This issue was best addressed in the Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives (GEMINI) trial of 1235 patients with hypertension (>130/80 mmHg) and type 2 diabetes; all patients were treated with an ACE inhibitor or ARB, while other antihypertensive drugs were discontinued [68]. The patients were then randomly assigned to carvedilol (6.25 to 25 mg twice daily) or metoprolol (50 to 200 mg twice daily); hydrochlorothiazide and a dihydropyridine calcium channel blocker were added as necessary to achieve a blood pressure below 130/80 mmHg.
Carvedilol was associated with the following significant benefits at five months; the blood pressure was similar in the two groups:
●No change in glycated hemoglobin (A1C) compared with a mean 0.15 percent increase with metoprolol and an increase in insulin sensitivity (9.1 percent) and compared with no change with metoprolol. In addition, fewer patients withdrew from the trial because of worsening glycemic control (0.6 versus 2.2 percent).
●A lower rate of progression to moderately increased albuminuria in patients in whom this was not present at baseline (6.6 versus 11.1 percent with metoprolol) and a 16 percent relative reduction in albumin excretion.
The modest worsening of glycemic control seen with metoprolol has also been noted in studies of other beta blockers [70-72].
In the United Kingdom Prospective Diabetes Study (UKPDS) study of patients with type 2 diabetes, atenolol was as effective as captopril in terms of both blood pressure lowering and protection against microvascular disease [73]. In the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) diabetic parallel study, however, losartan provided significantly more protection from adverse cardiovascular outcomes than atenolol [74].
Patients with heart failure — Heart failure is common in patients with diabetes. Those who have heart failure with reduced ejection fraction (HFrEF) are typically treated with renin-angiotensin system inhibitors (ACE inhibitors, ARBs, or angiotensin receptor-neprilysin inhibitors [ARNIs]) whether or not they have albuminuria, since these drugs reduce mortality and morbidity in the setting of HFrEF. Patients who have heart failure with preserved ejection fraction (HFpEF) are often prescribed mineralocorticoid receptor antagonists because these agents may reduce morbidity in that population. Frequently, patients with HFpEF require multiple antihypertensive medications to control their blood pressure, and among those with diabetes, agent selection should follow the same approach as described above. (See 'Overview of our approach' above.)
Detailed discussions of pharmacologic therapy in patients with heart failure are presented elsewhere:
●HFrEF (see "Initial pharmacologic therapy of heart failure with reduced ejection fraction in adults" and "Secondary pharmacologic therapy in heart failure with reduced ejection fraction (HFrEF) in adults")
●HFpEF (see "Treatment and prognosis of heart failure with preserved ejection fraction")
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Hypertension in adults" and "Society guideline links: Diabetes mellitus in adults".)
SUMMARY AND RECOMMENDATIONS
●Contributors to hypertension in patients with diabetes include kidney disease, extracellular fluid volume expansion, and increased arterial stiffness. Hypertension is common problem in patients with both type 1 and type 2 diabetes, but the time course in relation to the duration of diabetes is different. In type 1 diabetes, the prevalence of hypertension at the time of diagnosis is low, increasing subsequently over several decades. In type 2 diabetes, a substantial proportion of patients already have hypertension at the time of diabetes diagnosis. (See 'Pathogenesis' above and 'Epidemiology' above.)
●In general, patients with diabetes are at higher cardiovascular risk compared with the general population, and therefore we target more intensive, rather than less intensive, blood pressure control. Our recommendations on goal blood pressure in hypertensive patients with diabetes mellitus are presented in detail elsewhere. Goal blood pressure also depends upon the method by which it is measured (table 1). (See "Goal blood pressure in adults with hypertension", section on 'Patients with diabetes mellitus'.)
●Nonpharmacologic interventions should be prescribed, as appropriate, to all patients with hypertension. These include salt restriction; weight reduction; increased consumption of fresh fruits, vegetables, and low-fat dairy products; increased exercise; and avoidance of smoking and excess alcohol ingestion.
●The decision to initiate drug therapy should be individualized and involve shared decision-making between patient and provider. In general, however, we initiate antihypertensive drug therapy in patients with diabetes who have an out-of-office daytime blood pressure ≥130 mmHg systolic or ≥80 mmHg diastolic (or an average of appropriately measured office blood pressures ≥130/80 mmHg if out-of-office readings are not available). (See 'When to initiate antihypertensive drug therapy' above and "Overview of hypertension in adults", section on 'Who should be treated with pharmacologic therapy?'.)
●Our approach to the choice of antihypertensive therapy depends in part upon the degree of the patient's urine albumin excretion (see 'Overview of our approach' above and "Treatment of diabetic kidney disease", section on 'Severely increased albuminuria: Treat with angiotensin inhibition'):
•In patients with severely increased albuminuria, ≥300 mg/day (formerly called "macroalbuminuria" and sometimes called "very high albuminuria"), we treat with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) as part of the regimen to achieve the blood pressure goal. (See 'Severely increased albuminuria (300 mg/day or higher)' above.)
•We also use these drugs in patients with moderately increased albuminuria (formerly called "microalbuminuria" and sometimes called "high albuminuria") who are hypertensive, even though the benefits of angiotensin inhibition on kidney disease progression in such patients are unproven. (See 'Moderately increased albuminuria (30 to 299 mg/day)' above.)
•In patients without increased albuminuria, initial monotherapy can consist of an ACE inhibitor, ARB, thiazide diuretic, or calcium channel blocker. However, because thiazide diuretics have the disadvantage of an adverse effect on glucose metabolism, albeit minor, many experts will choose an ACE inhibitor, ARB, or calcium antagonist as initial therapy. (See 'Normoalbuminuria (less than 30 mg/day)' above.)
•In patients whose blood pressure is >20/10 mmHg above their goal, initial combination therapy (with a single pill, if available) should be prescribed. In addition, among patients with diabetes initiated on monotherapy, a second agent will often be required to attain goal blood pressure. In these settings (ie, when two antihypertensive drugs are needed), we generally treat with an ACE inhibitor or ARB plus a long-acting dihydropyridine calcium channel blocker. (See "Choice of drug therapy in primary (essential) hypertension".)
●If an ACE inhibitor or ARB is indicated but cannot be used, alternative first-line agents include calcium channel blockers and diuretics. However, in patients with severely increased albuminuria, nondihydropyridine agents (eg, diltiazem, verapamil) are generally preferred over dihydropyridine drugs (eg, amlodipine, felodipine), since nondihydropyridine calcium channel blockers can reduce albuminuria. (See 'Overview of our approach' above.)
●The choice of initial antihypertensive therapy may vary from the approach described above if the patient has one of the following disorders: a recent myocardial infarction (ie, in the previous three years), in which case a beta blocker is appropriate, or heart failure, in which case various antihypertensive agents may be appropriate regardless of the degree of albuminuria. (See 'Indications for alternative antihypertensive drugs' above.)
