To investigate whether concomitant treatment with Lokelma can improve the efficacy of standard blockade of the renin-angiotensin system in patients with type 2 diabetes, diabetic nephropathy and hyperkalemia.

Patients with type 2 diabetes and nephropathy, especially patients with impaired kidney function, frequently encounter hyperkalemia as an adverse effect of RAAS blocking treatment. Consequently, RAAS blocking treatment is reduced or discontinued, which in turn impairs prognosis in terms of long-term renal and cardiovascular outcome. Not only can hyperkalemia as an adverse event lead to changes in RAAS blocking treatment, the presence of persistent potassium levels in the upper part of the normal range can impair the efficacy of the RAAS blocking treatment, another reason to expect a beneficial effect of Lokelma treatment.

The study is a multicentre (3 sites in Sweden (TBD), 2 sites in Denmark (Steno Diabetes Center Copenhagen and Zealand University Hospital, Roskilde), double-blind, randomized placebo-controlled, parallel study. The study drug is compared to matching placebo that cannot be distinguished from active drug. The treatment period is 12 weeks.

Inclusion Criteria:

1. Provision of informed consent prior to any study specific procedures
2. Female and/or male patients with type 2 diabetes aged 18-85 years
3. Persistent macroalbuminuria (UACR ≥ 200 mg/g in at least two out of the three latest UACR measurements in subject history).
4. Chronic (at least 1 month) stable RAAS blocking treatment, i.e maximum tolerated (individually defined by investigator) dose of an ACE inhibitor or ARB at time of inclusion.
5. Documented hyperkalemia (plasma potassium ≥ 5.0 mmol/l) at least once in the 90 days prior to inclusion in the study.
6. Negative pregnancy test (urine or serum) for female subjects of childbearing potential.
7. Female subjects must be 1 year post-menopausal, surgically sterile, or using an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign consent) and for 3 months after the last dose of Lokelma/matching placebo to prevent pregnancy. In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used.

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both Investigator staff and/or staff at the study site)
2. Previous enrolment in the present study
3. Use of potassium-lowering agent (loop-diuretics not included)
4. Participation in another clinical study with an investigational product during the last 3 months prior to inclusion.
5. Plasma potassium < 3.5 mmol/l within the previous six months before inclusion.
6. Known hypersensitivity to Lokelma
7. Known history of drug or alcohol abuse within 1 year of screening
8. Estimated glomerular filtration rate (eGFR) <15 ml/min/1.73 m2 (calculated by CKD-EPI formula).
9. History of long QT syndrome.
10. For women only - currently pregnant (confirmed with positive pregnancy test) or breast feeding.